1、REPORTThe brave new world of synthetic biology2024Major impacts,significant challenges Richard Feynman,theoretical physicist“What I cannot create,I do not I do not understandunderstand.”3Blue Shift /REPORT 005The brave new world of synthetic biologyMajor impacts,significant challengesAuthorsDr.Alber

2、t Meige,Director of Blue Shift,Arthur D.LittleRick Eagar,Partner Emeritus,Arthur D.LittleDr.Ulrica Sehlstedt,Managing Partner,Arthur D.LittleDr.Franziska Thomas,Partner,Arthur D.LittleCamilla Hanna,Program Manager of Blue Shift,Arthur D.LittleSimon Norman,Manager,Arthur D LittleMin Ji Kim,Manager,Ar

3、thur D.LittleClaudia Nichterlein,Manager,Arthur D.LittleNick Bloser,Business Analyst,Arthur D.Little Artist-in-residenceC-LABPhilosopher-in-residenceDarian Meacham,Maastricht UniversityCONTENT-CONTENT-CONTENT-CONTENT-5Executive summary 6Preamble 101.What is synthetic biology&why is it important?122.

4、The scientific&technical landscape 24Interlude#1:Evolving aesthetics Intersecting art&science in the language of cells 363.The applications&industry landscape 44Interlude#2:Philosophicalðical issues surrounding SynBio 664.How companies should respond 68Conclusion:Companies need to be ready for gr

5、owth 74Appendix 1:Example SynBio tool&technology players 80Appendix 2:Example SynBio application players 866Blue Shift /REPORT 005Executive summary While the 20th century was in many ways the century of the industrialization of chemistry,the 21st century is promising a similar revolution in biology.

6、The revolutions foundation began with the discovery of DNA in the 1950s and expanded to core technologies that help to understand,analyze,and manipulate our genetic codes as well as the proteins and,ultimately,the cells and organs that underlay human biology and extend to the universe surrounding us

7、.These findings have led to numerous groundbreaking discoveries and the expanding potential to understand,detect,and treat diseases.We are also increasingly seeing biological systems used outside of the life sciences in a wide range of fields.In recent years,the discussion increasingly has centered

8、on synthetic biology,or SynBio,a term coined in the 1980s when scientist Barbara Hobom used it to describe bacteria that had been genetically engineered using recombinant DNA technology.The term has evolved significantly since then to be used more broadly and sometimes controversially.While SynBio h

9、as already increased our understanding of biological systems and led to the availability of new tools for their manipulation and diagnostics,more recent advances in computing power and development of tools such as artificial intelligence(AI)and machine learning(ML)are leading to a further rapid acce

10、leration 7Blue Shift /REPORT 005in innovation.The impacts have the potential to be disruptive across many industry sectors not just healthcare and life sciences and food and agriculture,but also industrial,chemicals,manufacturing,consumer goods,energy,and IT.With this increasing impact across multip

11、le disciplines and ecosystems comes an expanding need for communication and critical discourse around the implications of SynBio for society.While SynBio offers the potential to generate foods like milk or meat without animals and their associated environmental impact,we require better regulation to

12、 control quality and safety and need to understand the global and economic implications in this field.Recent examples such as the HeLa cell case and the debates around golden rice or what we are allowed to call“milk”show that we need to better address some basic questions:Who owns a gene or a cell?W

13、hat level and speed of change are we willing to accept as a society?What are the risks of these new technologies?While gene and cell therapy offer the opportunity to cure serious and debilitating diseases such as muscular dystrophy or hemophilia,innovations are already enabling,for example,the synth

14、etic creation of human embryos.What implications do these have for our future development?Based on extensive Arthur D.Little research supported by surveys and interviews with 28 global experts in SynBio technology and applications,this Report aims to provide a comprehensive overview of the current s

15、tatus and prospects for SynBio,including what it comprises,the present state of technological developments,the existing development market and key player landscape,current and prospective applications,and how businesses should prepare for the future.Overall,we conclude that:-SynBio is an extremely d

16、iverse field.SynBio is unique in the breadth of its potential applications from healthcare to food,manufacturing,industrial processing,and even the digital industries.The maturity of its technologies range from the embryonic to the fully commercialized.In considering its prospects,it is important to

17、 take a sufficiently granular approach.-SynBio technologies could have massive transformational impact in a 20-year time frame.Technologies like predictive genetic engineering,DNA synthesis for complex organisms,DNA-based storage,and AI-powered applications could transform our industries,our ability

18、 to engineer living systems,and how we cope with climate change.SynBio is unique in the breadth of its potential applications.-Many SynBio applications are poised for growth.Forecast growth rates for SynBio are 20%CAGR to 2030 overall,especially in healthcare and life sciences and food and agricultu

19、re.Drivers for growth are strong,both in terms of technology push(increasing investment,lower technology costs,growing ecosystems)and market pull(especially sustainability,healthcare needs,and manufacturing efficiency).The current market is predicted to grow from around US$15 billion in 2023 to$70 b

20、illion by 2030.Perhaps more importantly,if currently developing SynBio technologies mature successfully,SynBio could have a huge impact,disrupting sectors comprising as much as 15%-20%of the entire global output in several areas in the coming decades,including:-Healthcare and life sciences.A large r

21、ange of application areas enable personalized and potentially curative treatments as well as improvements in diagnostics and drug design and development.In the future,we expect more sophisticated treatments,greater protection from more diseases,and new applications for degenerative and genetic condi

22、tions.-Food and agriculture.Applications are extensive,ranging from crop domestication to synthetic food and bioremediation,with further developments in all these areas expected in the coming years.-Industrial and consumer goods.Applications include novel/specialty products,raw material replacements

23、,sustainability,and process performance improvement.-Energy.Applications include biofuels,bioelectricity,bio-batteries,remediation,and process improvement for traditional fuels.-IT and tech sector.DNA-based data storage is the most promising research area but is still only at the proof-of-concept(Po

24、C)stage.-Challenges and barriers remain high with several critical uncertainties.In many SynBio applications,development has been ongoing for decades,often driven more by technology push than market pull.Critical uncertainties include skill/competency gaps,achieving standardization of toolsets and s

25、ystematization of the knowledge base,adverse public perception,ethical/biosecurity issues,availability of funding and investment,difficulties in scaling up to production levels,and poor economics compared to conventional technologies,which could hinder market growth.8Blue Shift /REPORT 005In many Sy

26、nBio applications,development has been ongoing for decades.-Companies should ensure a suitable SynBio strategy is in place.Given strong drivers,accelerating technology developments,and potentially huge impacts,companies should be prepared for exponential growth that could result from breakthroughs.G

27、iven its diversity,companies need to consider carefully which fields are relevant for their business and conduct realistic market-based assessments.Key steps include:1.Identify potential opportunities.Pinpoint those areas of the business that could be disrupted,or new opportunities created,by curren

28、t or envisaged future SynBio technologies.Consider how SynBio could enhance current performance,enable new products or processes,enhance sustainability,and/or improve efficiency or customization.2.Assess attractiveness and develop strategy.Take a market-led approach to assessing potential business c

29、ases and develop a scenario-based strategy,considering the barriers to be overcome and the critical uncertainties that remain.3.Develop capabilities.Understand where and how to bring together the required capabilities within the ecosystem.This is especially important given SynBios multidisciplinary

30、nature and shortages of specialist skills.4.Maintain ecosystem presence.It is vital to engage in regulatory and ethical discourse and respond rapidly if and when applications become exponential.9Blue Shift /REPORT 005Companies should be prepared for exponential growth that could result from breakthr

31、oughs.PreambleI am a fan of technology.Yet at the same time,I am extremely concerned about its negative externalities.Negative externalities on our children,on society,on our institutions,or on our businesses.Blue Shift /REPORT 00510This concern is not new.In fact,I particularly remember reading Bra

32、ve New World by Aldous Huxley in high school as a teenager.In this novel,Huxley presented a seemingly wonderful world where a mix of totalitarianism and technology resulted in an extremely stable global society without war or conflicts.By all appearances,it was the best of all possible worlds.Howeve

33、r,individual freedoms and free will almost completely disappeared.That was my introduction to technological ambivalence.While preparing this Report on synthetic biology with the Blue Shift team,Huxleys Brave New World came back to me like a genetically modified“madeleine de Proust,”and I could not h

34、elp but think about all the dystopian scenarios.Why?Because SynBio encompasses a multitude of potential threats and negative impacts that could arise from its misuse or unintended consequences:deadly pathogens,gene drive(which can be used to propagate a particular suite of genes throughout a populat

35、ion)technology,environmental and health risks,or the DIY biology movement(a movement of citizen scientists interested in SynBio experiments,which raises concerns about the misuse of easily accessible and low-cost technologies like CRISPR defined as clustered regularly interspaced short palindromic r

36、epeat by individuals with little prior knowledge of the field).And the list goes on!But at the same time,I am totally amazed by the fact that most any industrial sector could leverage SynBio not just life sciences.In this Report,we focus primarily on the positives SynBio will bring to business,socie

37、ty,and humans.Before diving into it,I would like to share with you another very intriguing anagram:As always,anagrams move in mysterious ways.Albert Meige,PhD“Synthetic biology”transforms into“hit by Scientology”11Blue Shift /REPORT 00512CHAPTER12113WHAT IS SYNTHETIC BIOLOGY&WHY IS IT IMPORTANT?1Wha

38、t is synthetic biology&why is it important?Mankind has long questioned the nature of life,endlessly exploring the topic through religion,philosophy,art,and science.Since the mid-20th century and the discovery of DNA,the field of SynBio has provided insights into some of the“big questions”(see Figure

39、 1).Blue Shift /REPORT 00514For example,SynBio has shown that we can synthetically create new and different functions in living organisms and harness living cells to perform nonbiological tasks.In 2023,researchers at the Weizmann Institute of Science,Israel,claimed to have grown an entity that close

40、ly resembles a 14-day human embryo,without using sperm,eggs,or a womb.1Defining SynBioToday,definitions of SynBio vary but most center on the basic concept of engineering biological systems for useful purposes.Examples include:-“The design and construction of new biological parts,devices,and systems

41、,and the redesign of existing,natural biological systems for useful purposes”(Nature)-“A field of science that involves redesigning organisms for useful purposes by engineering them to have new abilities”(US National Human Genome Research Institute)-“The use of modern technologies and computation to

42、 engineer biology to solve problems related to the environment and human health”(University of California San Diego UCSD Synthetic Biology Institute,USA)-“A multidisciplinary field of science that focuses on living systems and organisms,and it applies engineering principles to develop new biological

43、 parts,devices,and systems or to redesign existing systems found in nature”(Wikipedia)1 Gallagher,James.“Scientists Grow Whole Model of Human Embryo,Without Sperm or Egg.”BBC News,6 September 2023.Fig 1 How SynBio aids in answering fundamental questions about life Note:(1)Biomimetics is the study&de

44、sign of artificial systems that mimic the formation,structure,function,or processes of natural ones Source:Arthur D.LittleNote:(1)Biomimetics is the study&design of artificial systems that mimic the formation,structure,function,or processes of natural onesSource:Arthur D.LittleFig 1 How SynBio aids

45、in answering fundamental questions about life Can life be created synthetically?The Genome Project-write project seeks to write the first complete human genome,although full bottom-up creation of a novel living system has not yet been achievedShould we equate living things to their functions?Using c

46、ells as factories to create chemicals&proteins,manipulating cells to generate energy,or conversely,creating solar panels out of organic material capable of replicating photosynthesis in plantsDoes being alive necessarily imply being in physical form?Using DNA for high-density data storage is almost

47、at PoC stage;biocomputers,using a 3D culture of human brain cells,may in future offer a low-energy,higher-performance alternative to conventional computing,enabling both Is life more than the sum of its constituent parts?Current exploratory research is developing tools that enable the mapping of the

48、 molecules&wiring of the brain,the recording&control of its neural dynamics&the repair of its dysfunctionQUESTIONHow new functions can be created in living organisms,suggesting we can approximate the creation of,at least,aspects of“life”How living organisms can be repurposed to provide different fun

49、ctions&artificial systems can mimic natural ones(biomimetics)1Biocomputers,which blur the lines between biological information systems(in vitro,with genetic code&neurological states)&artificial information systems(in silico,with software code)Improved understanding of living systems behaviors at the

50、 genetic&cellular level(although biological systems show complex emergent behaviors,which are hard to model)WHAT SYNBIO HAS EXPLOREDEXAMPLES15Blue Shift /REPORT 005A 2023 Blue Shift global expert survey2 carried out as part of this Report explored what distinguishes SynBio from related fields.It fou

51、nd that experts commonly identify convergence,engineering principles,and systems thinking as key features(see Figure 2).While opinions broadly concur with these three aspects,experts do not fully agree on whether the source materials must be living organisms or if they can be created synthetically.F

52、or the purposes of this study and its ultimate focus on applications and impacts,we concluded that it is more useful to define the field in terms of what it produces and how it works,rather than the nature of its raw materials.We therefore propose a practical definition of SynBio that embodies the f

53、ollowing key features:“Engineering,modifying,or creating novel living or hybrid3 biosystems for useful purposes.”Supporting this definition,SynBio involves three features:1.The convergence of multiple disciplines -Bridging life and physical sciences-At the boundary between naturally occurring and ar

54、tificial worlds-Living or hybrid systems-Biomimetic engineering approaches can also be part of the SynBio toolbox,although mimicking biological systems is not a SynBio aim,per se2 Survey comprised responses from 38 academic and industry leaders from around the world.3 Hybrid:systems that combine org

55、anic and inorganic materials.Fig 2 Expert views on what SynBio coversSource:Arthur D.LittleSource:Arthur D.LittleFig 2 Expert views on what SynBio covers“The engineering of biology to design,build,test&learn new functionalities”“The construction of biological systems from smaller parts,in a modular

56、way”“Distinguished from biochemistry by the toolset”“Originating from systems biology,but now with enough data to build models”“Multidisciplinary investigation of how to make new forms of life”“Characterizing parts&systems to increase future predictability in design”“Purposeful,intentional,rational

57、design of gene modification&expression,or new functions,systems,organisms”“Predictable,controlled,precise engineering of new functions in a variety of living systems”“Synthesis i.e.,methods of composing&putting together for living systems”“The purpose of understanding nature or producing useful biol

58、ogical machines”“Inspired by nature where the answer to all problems already exists in nature”“Modifying or creating living systems entirely from materials that never were alive or part of a living organism”“The creation of new living systems by design”CONVERGENCE OF MULTIPLE DISCIPLINES&FUNDAMENTAL

59、 BLURRED LINESENGINEERING PRINCIPLES:APPLIED,BEYOND ANALYSISSYSTEMS THINKING&MODULARITY:COMPLEX SYSTEMS DESIGNQUESTIONIn your words,what is synthetic biology?How is it distinguished from related fields?16Blue Shift /REPORT 0052.Applied engineering principles -Intentional engineering of living system

60、s to achieve specific goals and functionalities3.Systems thinking and modularity-Decomposition of biological systems into interchangeable modules-Understanding how individual parts behave and interact within the overall systemThe spectrum of SynBio applicationsSynBio covers a wide range of potential

61、 applications(see Figure 3),characterized by their degree of novelty,from more basic enhancement of existing capabilities to the complete creation of entirely new living systems.At the next level of detail,it is useful to split the functionalities of SynBio into categories across three broad aims(se

62、e Figure 4).As Figure 4 illustrates,SynBio can be used for making completely new products(biological and nonbiological),enhancing the performance of existing products,and improving production and manufacturing processes for the same products.In the latter category,improved sustainability is an impor

63、tant benefit,although better efficiency and precision are also key.Fig 3 The SynBio application spectrum Source:Arthur D.Little;UK Research and Innovation(UKRI);Davies,Jamie A.Synthetic Biology:A Very Short Introduction.Oxford University Press,2018;Benner,Steven A.,and A.Michael Sismour.“Synthetic B

64、iology.”Nature Reviews Genetics,Vol.6,July 2005Source:Arthur D.Little;UK Research and Innovation(UKRI);Davies,Jamie A.Synthetic Biology:A Very Short Introduction.Oxford University Press,2018;Benner,Steven A.,and A.Michael Sismour.“Synthetic Biology.”Nature Reviews Genetics,Vol.6,July 2005Fig 3 The S

65、ynBio application spectrum ENHANCEMENT Enhancing an organisms existing functionality(e.g.,increasing photosynthetic capacity of algae or plants to boost growth&biomass production)AUGMENTATION Augmenting an organism with another function or combination existing in nature(e.g.,modifying bacteria with

66、parts from other organisms to produce enzymes that can break down plastic waste)FUNCTION CREATION Creating an entirely new function in an organism that does not already exist in nature(e.g.,genetically modified mosquitoes that are unable to transmit diseases like malaria or dengue fever)LIVING SYSTE

67、MS CREATION Creating entirely new living systems using either living or nonliving parts,such as xenobots composed of skin cells&heart muscle cells,both of which are derived from stem cells harvested from early-stage frog embryosDEGREE OF NOVELTY 17Blue Shift /REPORT 005What drives advances in SynBio

68、?Although SynBios origins go back to the 1950s,breakthroughs have accelerated considerably over the last 20 years,as shown in the timeline in Figure 5.Over the last decade,SynBio progress has further accelerated due to both technology push and market demand:-Technology push convergence between ongoi

69、ng developments in life sciences and physical sciences(see Figure 6),including more powerful and accurate gene-editing tools-Market demand the need to meet growing demands for:-Greater sustainability(e.g.,renewable raw materials/energy)-Improved healthcare(e.g.,faster,lower-cost drug development;imp

70、roved diagnostics;more targeted therapies)-Greater food security(e.g.,improving yields at time of climate change and population growth)-Innovation(e.g.,more tailored products,transformative advances in computing,and other radical new applications)Fig 4 The aims of SynBio Source:Arthur D.Little,UKRIS

71、ource:Arthur D.Little,UKRIFig 4 The aims of SynBio AIMSEXAMPLES02.Enhanced performance of existing products Crop domestication&expedited plant breedingGene&cell therapies in cancer treatment01.Novel products&materials BiologicalNon-biological Synthesized foodsBioactive compounds as drug modalities o

72、r for drugsEnhanced natural fertilizers New life formsBiosensorsBio-batteries&fuel cellsSynthetic leather&rubberBiological computers&neural networks03.More sustainable&efficient manufacturing processesMore sustainableMore efficient/preciseBio-based manufacturing processesBio metals extractionWaste r

73、eduction&recyclingBioremediation Vaccine developmentBiosynthesis using novel enzymesPrecision fermentation using“whole”microbesSpecifically tailored foods&ingredients 18Blue Shift /REPORT 005Fig 5 SynBio milestones Source:Arthur D.LittleSource:Arthur D.LittleFig 5 SynBio milestones 1950s Discovery o

74、f the double helix structure2000s New developments in DNA synthesis&sequencing2005 First synthetic genome of a bacteriophage created2012 Discovery of CRISPR/Cas9 genome-editing technique,enabling the editing of individual genes2019 Creation of first bacterial genome entirely by computer2020 Creation

75、 of first xenobots(synthetic life-forms designed to perform a particular function);rollout of mRNA-based vaccines against COVID-191970s Discovery of restriction enzymes&invention of recombinant DNA technology1980s First biologic produced in mammalian cells approved in 1986 by Genentech(Activase)1990

76、s Launch of the first gene therapy trial2017 First genetically modified T-cell therapy approved in the US2021 Deep learning technology breakthrough in protein folding prediction&antibody discovery1960s:Pioneers of synthetic biology Jacob&Monod postulated how cellular regulation could enable assembly

77、 of new systems from molecular components2012:Commercial biomanufacturing protein therapy in plant cells2014:Illumina launches next-generation sequencing(NGS)technology,greatly increasing throughput,scalability&speed&claimed to outpace Moores law2017:FDA approves CAR T,which has been shown to cure c

78、ertain blood cancer conditions1980s:Genetically modified insulin engineered using bacteria to produce insulin(“Humulin”)with help of recombinant DNA2000:First synthetic biological circuits designed by humans the genetic toggle switch&the repressilator proved that gene regulatory networks could be de

79、signed from mathematical principles2004:First international conference on synthetic biology“Synthetic Biology 1.0”(Massachusetts Institute of Technology)2020:DNA Data Storage Alliance formed to create&promote interoperable storage ecosystem based on DNA as data storage medium;celebrated 50th member

80、in 2002Fig 6 Technology push drivers for SynBio Source:Arthur D.LittleSource:Arthur D.LittleFig 6 Technology push drivers for SynBio SynBioLife sciencesBiology,chemistry,biochemistry,cell biology,protein science,metabolic engineering,advanced fermentation,biotechnology,genome editing,epigenetics,com

81、putational biology,neurosciencePhysical sciencesPhysics,nanotech,materials science,surface science,computer science,AI,materials science,surface science,mathematics,data science,robotics/IoT,simulation/digital twinAnalytic biologyGreater understanding of fundamental biological processes,particularly

82、 with advent of omics approachesEngineering principlesPrinciples such as“design build,test,learn”changed SynBio from an analytical pursuit to a new type of engineering discipline Systems biologyGreater understanding,systematizing&engineering of more complex biological systemsBig data&AIAvailability

83、of“big bio”data&standardization of use of AI/black box modeling technologies enabled better design,supported by data engineering principlesIncreasing capabilities&collaborations(toolset/platform/application developers,service providers)Lower costs for DNA sequencing,gene synthesis&editingIncreasing

84、private&public investmentLast decade19Blue Shift /REPORT 005This combination is driving increasing public and private investment and partnerships across SynBio ecosystems.Examples within the US include:-US government SynBio research funding increased to$161 million in 2022,with public funding totali

85、ng$820 million over the last five years.-The US private sector invested$8 billion in SynBio in 2022.-Institutions including Northwestern University,USA,and the Massachusetts Institute of Technology(MIT),USA,have received grant awards for SynBio research projects involving interdisciplinary teams.-Ne

86、w government-sponsored collaborations have launched,such as the SynBio partnership involving Ginkgo Bioworks,Geno,and Antheia.-New consortia have formed to develop cross-platform solutions.For example,Microsoft,Lenovo,and Twist Bioscience are collaborating to explore cross-platform work,such as thro

87、ugh the potential of DNA data storage.Increased activity is fueling predicted growth of the global SynBio market of 24%CAGR to over$70 billion in 2030,from around$15 billion in 2023(see Figure 7).This covers just the provision of services,tools,know-how,and products to enable the application of SynB

88、io by end users in markets such as healthcare,food,and industry.It does not include any potential incremental revenue these end users may realize using SynBio tools,the impacts of which we outline in the final part of this section and in Chapter 2.Fig 7 Predicted global SynBio market growth 2022-203

89、0 Source:Arthur D.LittleSource:Arthur D.LittleFig 7 Predicted global SynBio market growth 2022-2030$12.5$15.5$19$24$30$37$46$57$70in US billion dollars+24%20282022202320262024202520272029203020Blue Shift /REPORT 005Challenges to SynBio growthDespite demonstrating impressive growth potential,SynBio d

90、evelopment faces large-scale obstacles.These are wide ranging,from biosecurity/ethical issues to technical,economic,and consumer challenges.Biosecurityðical issuesAltering biological organisms or creating completely new ones raises biosecurity challenges around potential unintended environmental

91、consequences,or the deliberate misuse of SynBio by bad actors.It also leads to an ethical debate around what is deemed acceptable when it comes to changing or creating forms of life,and a blurring of the boundaries between“animate”organisms and“inanimate”machines,as detailed in Figure 8.Global regul

92、ation is central to both ensuring biosecurity and providing reassurance around ethical concerns,such as by adopting and enforcing key principles and codes of conduct with researchers,companies,and countries.However,regulations and guidelines are still evolving.Some overall principles have been defin

93、ed,such as the long-established and internationally recognized Convention on Biological Diversity(CBD).This includes provisions related to SynBio,for example,around ensuring the safe handling,transfer,and use of living modified organisms(LMOs)produced using SynBio techniques.However,these principles

94、 have yet to be consistently applied at a global regulatory level.Currently,fragmented national and regional regulatory frameworks equates to limited guidance over a coherent approach to the responsible use of SynBio.Fig 8 Key biosecurity and ethical issues around SynBio Source:Arthur D.LittleSource

95、:Arthur D.LittleFig 8 Key biosecurity and ethical issues around SynBio SynBio could be misused(e.g.,applied to create biological weapons or to pursue racial genomics)Manipulating organisms or creating new ones has the potential to cause harmful unintended consequences to the environment and/or to hu

96、man health if not contained,regulated&managedBlurring of the boundaries between organism&machine gives rise to issues around legal definitions of life;this could be even more complex with the advent of AI There are ethical issues around designing&creating new forms of life beyond what is traditional

97、ly considered the purview of human beings(e.g.,“designer babies”)MISUSEBIOSECURITYORGANISM OR MACHINE?“PLAYING GOD”21Blue Shift /REPORT 005Guidelines are also being developed around ethical issues.For example,codes of conduct,such as those set up for scientific research,have been created by organiza

98、tions like the International Society for Systems Biology(ISSB)and the Synthetic Biology Leadership Council(SBLC).Bodies such as the World Health Organization(WHO)are forming similar guidelines.However,along with the pace of emerging technologies,regulations are changing rapidly as well.This means th

99、at understanding and navigating different biosecurity and ethical issues remains a challenge for SynBio players.Technical,economic&consumer challengesAt the same time,there remain significant technical,economic,and consumer acceptance barriers when it comes to accelerating the use of SynBio in many

100、areas.These include the difficulties of scaling up processes from the lab to full production,poor cost-competitiveness with existing alternatives,a lack of sufficiently powerful technology,a need for large-scale investment,and potential consumer pushback at SynBio-derived products viewed as dangerou

101、s or threatening in some way(see Figure 9).Fig 9 Technical,economic,and consumer challenges to SynBio growth Source:Arthur D.LittleSource:Arthur D.LittleFig 9 Technical,economic,and consumer challenges to SynBio growth In several applications,scale-up from lab to production scale is both technically

102、&economically challengingMany SynBio-based manufacturing processes are not yet as cost competitive as traditional processesConsumer/public perception of SynBio-producedproducts is negative in some areas Some SynBio techniques&applications are limited by available technological capacities(e.g.,data m

103、anagement&computing power)Substituting SynBio for traditional industrial processes at scale may involve high capital cost&riskScale-upTransformation barriers Cost competitivenessConsumer/public perceptionTechnological capacitiesLarge-scale production&manufacturing of cell therapies Manufacture of ch

104、emical products from bio-based feedstocks instead of fossil fuelsGenetically modified foodsIn silico advances in drug discovery Bio routes to plastic polymers&derivativesEXAMPLE22Blue Shift /REPORT 005The transformative potential of SynBioWhile it currently faces significant challenges,SynBios poten

105、tial impact on end-user industries is vast.SynBio applications have the power to fundamentally change some of the largest industry sectors across the globe,helping solve critical challenges that threaten humanitys future,such as those around sustainability,health,and food supply.These industry secto

106、rs,including agriculture,healthcare,manufacturing,and data processing,represent about 15%-20%of the current global output,demonstrating SynBios potential significance if it can overcome the challenges and uncertainties outlined in the section above.Taking the example of the US,these disrupted sector

107、s make up around 20%of current GDP,covering approximately$5 trillion,as illustrated in Figure 10.Given this far-reaching and diverse potential,players in the sectors concerned cannot afford to ignore the ongoing progress of SynBio development especially in view of the increasing strength of the driv

108、ers on both the technology and market sides.Fig 10 SynBios potential impact on US GDP,2022 Source:Arthur D.Little,US Bureau of Economic AnalysisSource:Arthur D.Little,US Bureau of Economic AnalysisFig 10 SynBios potential impact on US GDP,2022$1,849Healthcare services$569Chemicals,plastics,including

109、 pharmaceuticals$468Manufacturing,including medtech$440Utilities$440Oil,gas,mining$374Data processing$327Food products244Agriculture$93Textile,apparel,paper$72Waste management21%of total US GDP$25.4 trillion$5,109Industries potentially impacted by SynBioIn US billion dollars23Blue Shift /REPORT 0052

110、4CHAPTER24225THE SCIENTIFIC&TECHNICAL LANDSCAPE2The scientific&technical landscapeAlthough boundaries can blur,the development landscape for SynBio can broadly be split into three groups(see Figure 11):1.Product developers creating customer products and applications that leverage SynBio know-how and

111、 toolsets 2.Tool&technology developers developing tools and technologies that enable SynBio products and applications,including techniques,hardware,software,and systems3.Underlying academic research creating basic and applied understanding of the science underpinning SynBioBlue Shift /REPORT 00526As

112、 with all models,the distinctions are not always clear.For example,some tool and technology players,such as Asimov and Arzeda,are also extensively involved in product development,often in partnership with product-based businesses.This section of the Report focuses on the academic research and tool/t

113、echnology development part of the stack.We cover product developers and applications in more depth in Chapter 3.Underlying academic researchAcademic research in SynBio is extensive and covers a wide range of domains,reflecting its multidisciplinary nature.US and European institutions currently lead

114、in investments in SynBio research,although investment in Asia is on the rise.Select examples of major academic players and their main areas of research include the following(illustrative only,non-exhaustive).US playersMIT Department of Biological Engineering Focusing on a wide range of relevant rese

115、arch for medical and life sciences applications,MITs centers include:-The Center for Multi-Cellular Engineered Living Systems a multidisciplinary group studying purpose-driven living systems with multiple interacting living components-The Center for Biomedical Innovation develops new approaches to b

116、iomedical technology,such as the structure and function of biomembrane proteins for applications in sensors-The Center for Neurobiological Engineering focuses on new tools for experimental investigation of the nervous system and engineering neurons,neural tissue,and their interactions with cells,dev

117、ices,and prostheticsFig 11 SynBio development landscape Source:Arthur D.LittleSource:Arthur D.LittleFig 11 SynBio development landscape Product developersTool&technology developersDesignBuildAnalyzeEnable Underlying academic researchBasic researchSocial/ethical Applied R&DCreating customer products&

118、applications that leverage SynBio know-how&toolsets Developing SynBio toolsets(tools&technologies that enable products&applications,including techniques,hardware,software,systems)Creating basic&applied understanding of the science underpinning SynBioOverlap some toolset players are involved in produ

119、cts&vice versaCUSTOMERSConsumer goodsEnergy Healthcare&life sciencesFood&agricultureIndustry,manufacturing,chemicals&materialsIT&tech27Blue Shift /REPORT 005Northwestern University:Center for Synthetic BiologyThe Centers research is based around four themes:1.Cell-free systems biochemical engineerin

120、g with cell-free biology activating basic cellular processes(e.g.,translation)without live intact cells2.Mammalian systems developing novel platforms and therapeutic strategies based on custom-programming novel cellular functions3.Enabling technologies high-throughput experimentation tools that will

121、 allow the optimization and understanding of multi-component biosynthetic transformations,including work on engineering platforms,parallel expression of proteins,and computational analysis to identify design rules in the data4.Ethics and societal impact technology gaps in low-and middle-income count

122、ries,exploring the new bioethical questions that arise from SynBio development and developing ethical training for scientistsStanford University:Synthetic Biology&BioengineeringThese two programs explore broad-based SynBio research,including protein engineering,microbiome studies,systems biology,bio

123、informatics,metabolic engineering,neuroengineering,biomechanics,medical devices,medical imaging,molecular engineering,microscopy,biomaterials,tissue engineering,omics/genomics,gene therapy,microfluidics,agrobiology and plant health,frugal science,and bio policy.European playersSwitzerland:ETH Zurich

124、The SynBio group focuses on developing and applying the tools and methods of biological computing and synthetic biology in the mammalian context,based on three pillars:1.Fundamental,enabling technologies for precise manipulation and reprogramming of mammalian cells2.Applying these tools to unmet nee

125、ds in biotechnology and translational research3.Development of gene and cell therapies powered by biological computing28Blue Shift /REPORT 005Academic research in SynBio is extensive and covers a wide range of domains.UK:Imperial College Centre for Synthetic Biology Research focuses on novel methods

126、 to accelerate the design-build-test-learn cycle as well as multi/interdisciplinary research,including:-Computational modeling and ML approaches-Automated platform development and genetic circuit engineering-Multi-cellular and multi-organismal interactions(including gene drive and genome engineering

127、,metabolic engineering,in vitro/cell-free SynBio,engineered phages,and directed evolution)-Biomimetics,biomaterials,and biological engineeringThe College also hosts SynbiCITE,the UKs innovation and knowledge center,created to accelerate and promote the commercial exploitation of SynBio research and

128、engineering biology applications.This includes the London Biofoundry,aimed at designing,engineering,and functional characterization of synthetic DNA.Germany:Max Planck Research Network in Synthetic Biology The network comprises 20 research groups from nine Max Planck Institutes.Research clusters inc

129、lude enabling technologies,life-mimicking processes,and systems perspectives.Topics covered include:-Engineering of genetic systems for bottom-up SynBio-Design and implementation of microfluidic tools for bottom-up SynBio-Dynamic protocellular systems-Recombinant protein production via cell free exp

130、ressionAsian playersChina:Shenzhen Institute of Synthetic Biology Established in 2019 as the first institute of SynBio in China,the institute claims to have the worlds largest multidisciplinary team specialized in SynBio.Singapore:Synthetic Biology for Clinical and Technological Innovation(SynCTI)Es

131、tablished in 2014 as the focal research program for SynBio at the National University of Singapore(NUS),SynCTI operates as an interdisciplinary research core,interacting with other research programs within NUS and leveraging existing research capabilities in SynBio that have been developed through f

132、unding from local and international organizations.Korea:Korea Advanced Institute of Science and Technology Department of Biological Sciences The department declares a focus on genomics and nanotechnology,with an emphasis on research on human diseases and their molecular mechanisms,functional genomic

133、s and its application,and nano-biotechnologies and their application.29Blue Shift /REPORT 005Research focuses on novel methods to accelerate the design-build-test-learn cycle.Some key research themesLooking across the overall scientific landscape,several current SynBio research themes are expected t

134、o mature within five to 20 years with the potential for major impact to business and society.Examples include:-Wide-scale adoption of cell-free biomanufacturing(high impact,low uncertainty,mature within 5-10 years).The use of cell-free systems for biomanufacturing has the potential to become the new

135、 standard in SynBio.Further evolution requires overcoming the challenges of product creation beyond lab scale.Possible applications include the industrial production of green chemicals and novel products across biofuels,cosmetics,and pharmaceuticals.-Convergence of AI,SynBio,and automation(high impa

136、ct,low uncertainty,mature within 5-10 years).Within SynBio,AI offers potential in data mining,bioinformatics,and computational biology,such as for pattern and structure recognition in gene expression data,engineering of biological systems,metabolic engineering,experiment automation,self-driving labs

137、,outcome prediction,and reverse engineering.It offers the potential for step changes in workflow speed,accuracy,and effectiveness.-DNA synthesis at genome scale for eukaryotic organisms(high impact,low uncertainty,mature within 5-10 years).New technologies with the ability to synthesize and produce

138、large-scale,complex DNA sequences are under development,including molecular assembly and cloning methods,template-independent enzymatic synthesis,microarray,and rolling circle amplification techniques.Being able to create large DNA sequences at scale and low cost would have major impact on fields as

139、 varied as sustainable materials,data storage,drug delivery,and genome engineering to generate organisms with useful properties,such as heat-resistant plants.-Fungal SynBio(high impact,medium uncertainty,mature within 5-20 years).Advances in applying biotechnology to mycology and fungal genetics,wit

140、h advances in long read sequencing,makes it possible to generate high-quality fungal genome assemblies.Fungi have potential in a wide range of applications,such as within environmental remediation,fungal-derived food products,enzyme and other chemical production,sustainable biomaterials,fungal batte

141、ries,and many more.-3D bioprinting of complex animal and human tissue and organs(high impact,low uncertainty,mature within 10-20 years).3D-printing technologies can be deployed to assemble multiple cell types,growth factors,and biomaterials.While tissue reconstruction is already feasible,reconstruct

142、ion of complex organs still has many challenges.For example,heart functionalities like vascularization,mechanical load,and electrical signal propagation must be replicated.If successful,the technology offers the potential for bioartificial organ transplants as well as other medical interventions and

143、 treatments.30Blue Shift /REPORT 005The use of cell-free systems for biomanufacturing has the potential to become the new standard in SynBio.-Predictive genetic engineering for multicellular organisms(high impact,high uncertainty,mature within 10-20 years).Despite progress at bacterial and mammalian

144、 cell levels,programming of higher organisms is highly complex,requiring,for example,the delivery of gene editing cascades or the engineering of whole embryos.The ability to change the physiology of animals such as worms would open possibilities and applications across agriculture,biomedical,and the

145、 environmental domain,notwithstanding potential ethical issues.-DNA-based data storage(high impact,medium uncertainty,mature within 10-20 years).Low writing/reading speeds and high costs per byte stored are key challenges for DNA-based data storage technologies.Current research includes using DNA na

146、nostructures(as opposed to DNA sequences)and combinations of nanomaterials and biomolecules.Research has the potential to provide high capacity,long lifespan,and lower energy storage to meet rapidly growing data storage needs.Tool&technology developersTool and technology development can be categoriz

147、ed usefully in terms of the design-build-analyze-enable workflow,essentially a common development engine that is fundamental to all SynBio implementation.The landscape includes large,established players;start-ups;and academia.Figure 12 provides a summary of the main tools and technologies currently

148、in use or under development split across four categories:1.Design help model and simulate biological systems2.Build assist in construct biological systems3.Analyze help test and evaluate biological systems4.Enable accelerate the engineering process and,importantly,enable scale-up from lab to industr

149、ial production levelsFig 12 Key SynBio tools and technologies Source:Arthur D.LittleSource:Arthur D.LittleFig 12 Key SynBio tools and technologies Tools to model,simulate&design biological systems:Biological computer-aided design(BioCAD)software to visualize complex systemsGene&protein design tools

150、to enable rational design of biomolecules with desired functionsSimulation tools to predict biological system behavior through mathematical models&algorithms AI&ML platforms to enable novel&optimized synthetic biology designs Foundational technologies to construct precise synthetic biological system

151、s:Manufacture of custom DNA sequences,the first step in implementing a synthetic biology designDNA&gene delivery systems to enable the creation of new&custom functionsGenome engineering tools to enable design through the modification of existing genomesFermentation technologies to produce bio-based

152、drugs,chemicals,fuels&other products(as opposed to large-scale enablers)Analytical technologies to test&evaluate synthetic biological systems:NGS to ensure correct DNA&genome assemblyMass spectrometry to identify&quantify specific proteins or metabolitesHigh-content phenotypic imaging to monitor rea

153、l-time growth&morphology of engineered cellsFlow cytometry to evaluate the efficacy of synthetic CAR T-cell designs(e.g.,for treating cancer)Tools that accelerate synthetic biology innovation&industrial scaling:Automated engineering to enable scalable,reproducible,rapid&precise synthetic biology wor

154、kflowsCloud-based tools to enable remote experimentation,design&executionMicrofluidics to enable precise control over small-scale biochemical reactions&miniaturization of experimentsLarge-scale fermentation technologies that enable efficient production(e.g.,cell-free,modeling&monitoring tools)Design

155、Build AnalyzeEnable 31Blue Shift /REPORT 005The workflow is similar to that used in conventional non-bio technology development(design,build,test,manufacture),although there are differences.For example,the relative unpredictability of some SynBio processes,and the challenges of scaling up,mean that

156、tools used to analyze and enable are perhaps even more critical.Tool&technology maturityTools have varying maturity levels:-Design generally the least mature(see Figure 13).While core gene and protein design and simulation tools have reached high maturity with well-established key players,the full p

157、ower of AI and digital technologies remains untapped and will struggle to match demand for mature solutions.-Build generally more mature(see Figure 14).Core technologies such as de novo DNA synthesis and DNA/gene delivery systems are already largely commercialized,while genome-engineering tools(e.g.

158、,CRISPR)are still maturing but have high disruptive potential and are on the cusp of wider adoption.-Analyze generally the most mature(see Figure 15).Dominated by a few large players(e.g.,Illumina and Thermo Fisher),rising demand for next-generation sequencing(NGS)has helped drive adoption,with the

159、market continuing to grow rapidly.Fig 13 Design technologies TRL=technology readiness level Source:Arthur D.LittleTRL=technology readiness levelSource:Arthur D.LittleFig 13 Design technologies DesignTechnologyGene&protein design toolsSimulation tools for biological systemsDescription Enable rational

160、 design by employing computational algorithms for sequence optimization,protein modeling&structure prediction;empower researchers to modify genetic sequences&protein structures to enhance desired functionsPredict biological system behavior(e.g.,effects of newly introduced gene/protein on cell)throug

161、h mathematical models&algorithms;enable in silico design iterations,reducing reliance on costly&time-consuming wet lab experiments;simulate gene expression,protein interactions&metabolic pathways,guiding experiment designRemarksRelatively mature market with several companies offering gene&protein de

162、sign tools for variety of applications(e.g.,personal/homecare,materials,food ingredient development);research is ongoing for better elucidation(e.g.,protein function based on its sequence)Relatively mature,with several well-established players,but there is still extensive ongoing innovation&integrat

163、ion with other technologies such as AI/ML,especially around understanding the effects at a cellular level ChallengesLimited understanding of sequence-function relationships&protein folding dynamics complicates functional design;lack of standardized tools for integrating experimental data&computation

164、al models to improve accuracy of design Developing standardized simulation platforms or formats for data exchange&collaboration among researchers;standardized tools for incorporating biological data into simulation models are also lackingMaturity TRL 4-9TRL 2-9AI/ML platformsHarness large amounts of

165、 biological data to build new&improved models,expediting the design of novel synthetic biology systems;automated&data-driven iterative design&learning approaches enable faster&more precise design processes for complex synthetic systems&potentially more broadly across various phases of synthetic biol

166、ogy(e.g.,by substituting experiments by AI/ML);can handle complex data sets,uncover hidden patterns&generate novel hypothesesMarket is relatively new&while companies like TeselaGen&Asimov use AI platforms,technology is still evolving;Google/DeepMind is working on AI use cases in healthcare&life scie

167、nces(e.g.,protein folding)Technical capabilities still emerging,contributing to limited accessibility&standardization;access to high-quality&diverse biological data&understandingis limited,making training AI/ML models difficult;reliability&robustness of AI/ML-based design approaches cannot be ensure

168、d across different applicationsTRL3-532Blue Shift /REPORT 005 Fig 14 Build technologies TALENs=transcription activator-like effector nucleases;ATMPs=advanced therapy medicinal products;CHO=Chinese hamster ovary;CROs=contract resource organizations;CDMOs=contract development&manufacturing organizatio

169、ns Source:Arthur D.LittleBuildTechnologyManufactureof custom DNA sequencesDNA&gene delivery systemsDescription Generating defined DNA sequences in sufficient quantities to conduct research&engineering;new DNA would then be sequenced with approaches like NGS to ensure correct DNA has been generated;a

170、bility&advancement not only to synthesize&assemble DNA de novo but also to sequence result are critical;DNA will then be used to produce protein,which will in turn perform desired functionMethods to transfer synthetic DNA into target cells,creating new biological systems with custom functionalities&

171、properties;efficient&accurate delivery of synthetic DNA is critical to induce production of specific proteins,perform new functions&create new organisms with desirable traits;several delivery methodsexist,including viral vectors(e.g.,using viral DNA as carriers for the synthesized DNA)nonviral metho

172、ds(e.g.,using liposomes as carriers)&physical methodsRemarksThough de novo synthesis&assembly has been possible for decades,the technology is still evolving;costs have been reduced 10 x in the last decade;capacity has increased to 1 Mbp DNA from 100 bp&innovative solutions like NGS have been widely

173、adopted;DNA synthesis market valued at$3 billion in 2022&is projected to grow strongly at CAGR of 20%(20222030)Mixed maturity depending on the technology;some viral&nonviral gene delivery systems have been used for decades with many established players,but others are emerging with innovative approac

174、hes;significant innovation&research is ongoing,driven both by service providers&pharmaceutical companiesChallengesAccurate synthesis of DNA molecules decreases rapidly with length,necessitating costly&time-consuming assembly processes;limits to manufacturing capabilities of DNA with specific feature

175、s(e.g.,repetitive sequences)Immunogenicity&overall safety concerns,especially with viral vectors&LNPs;size and/or amount of DNA that can be delivered varies depending on system but can be limiting;targetability to specific cells or tissues,especially when physiological barriers are involvedMaturity

176、TRL 8-9TRL 4-9TALENs=transcription activator-like effector nucleases;ATMPs=advanced therapy medicinal products;CHO=Chinese hamster ovary;CROs=contract resource organizations;CDMOs=contract development&manufacturing organizationsSource:Arthur D.LittleFig 14 Build technologies cont Genome engineering

177、toolsFermentation/cell culture technologiesEnables precise modification of genetic information in biological systems;can be used to introduce alterations in genetic code(e.g.,adding,deleting,modifying genes)as well as regulating gene expression to create custom functionalities;examples include gene-

178、editing tools such as CRISPR-Cas,TALENs,zinc-finger nucleases&transposon technologies for targeted gene integrationAmong oldest biological applications;includes cultivation of cells to produce(express)compounds such as alcohol&complex proteins such as insulin or antibodies;with advancement of ATMPs,

179、this can also include production of mRNAs or cells as a product;build tools range from manipulation of cells&cell expression systems to media development&engineeringFast-evolving market,valued at$5-$6 billion in 2022&growing at CAGR of 18%-20%until 2030;primarily used in cell line engineering,geneti

180、c engineering,diagnostics,&drug discovery&development;market growth driven mainly by CRISPR-Cas9 technology,governmental funding&increase in genome engineering research;apart from upcoming start-ups,larger companies also showing interest in fieldMicrobial fermentation technology market alone expecte

181、d to grow at 5%-7%CAGR over next 10 years,from$32 billion in 2022 to$50-$52 billion in 2030;market growth driven by technology advancements&growing rate of outsourced biologics manufacturing to CROs/CDMOs,as well as increased overall drug production,demanding growth in microbial fermentation marketE

182、nsuring selectivity&safety by addressing off-target&off-tissue effect critical but difficult;complex regulatory&high safety requirements to use tools in human medicine&agriculture;technology is associated with high development costs,making applications expensive&potentially inaccessibleCertain expre

183、ssion systems such as yeast,E.coli,or CHO are relatively well understood;challenges mostly relate to developing more stable&chemically defined media as well as to further engineer cells to improve stability&productivity;newer areas such as stem cells or cell-free production still in PoC stageTRL 4-9

184、TRL 6-9Fig 15 Analyze technologiesSource:Arthur D.LittleAnalyzeTechnologyNGS&high-speed real-time PCRMass spectrometryDescription NGS is a high-throughput&high-speed technology for analysis of nucleic acidsHigh-speed real-time PCR is a fast&more precise technology to quantify target genes in real ti

185、me during polymerase chain reaction(e.g.,used for gene expression)Used to identify&quantify specific proteins or metabolites,which are indicators of the synthetic systems behavior at the molecular levelRemarksAnalytic tool market encompasses broad spectrum of technologies of which mass spectrometry,

186、imaging microscopy&flow cytometry are select few that are also key for synthetic biology;these capabilities have been well established&several players already exist in the marketDemand is surging,especially from the field of medicine&biological sciences;innovations have increased accuracy,cost-effec

187、tiveness&throughput&advancements are still being made(e.g.,data processing&analytics);AI/ML developments have also enhanced capabilities of analyzing biological dataChallengesHigh-throughput analytical tools generate vast amounts of data on biological systems,but limited computational infrastructure

188、&tools hinder efficient storage,processing&analysisIntegrating data from diverse modalities(e.g.,genomics,transcriptomics,proteomics)in synthetic biology is critical for a comprehensive understanding of biological systems,yet challenging due to the absence of standardized methodsMaturity TRL 8-9TRL

189、8-9High-content phenotypic imagingAdvanced imaging techniques allow monitoring growth&morphology of engineered cells,which helps identify optimal conditions&designs for a given application TRL 8-9Flow cytometryRapid analytical technology using lasers to analyze cells&can be used to evaluate the effi

190、cacy of synthetic(e.g.,CAR T-cell)designs,a promising immunotherapy approach for treating cancerTRL 8-933Blue Shift /REPORT 005-Enable varying maturity(see Figure 16).Automation and fermentation technologies are fairly mature and established,while cloud labs and microfluidics are low in maturity,wit

191、h most players being start-ups.However,cloud lab companies are creating strong partnerships with large industry players,indicating the possibility for widespread adoption and growth in the coming years.Source:Arthur D.LittleFig 16 Enable technologies EnableTechnologyAutomation technologiesCloud labs

192、Description Automation&robotics enable scalable,reproducible&rapid synthetic biology workflows;automated liquid handling especially is a key technology within field:as experiments often require handling different volumes of liquids,these machines ensure precise dispensing of liquid volumes&enable fu

193、lly automated workflows,minimizing need for human interventionAutomated,centralized facilities for remote experiments;maximize efficiency by enabling remote experimentation,streamlined data management&global collaboration;scientists also freed from need to physically be present in the lab&empowered

194、to focus on creative decision-makingRemarksLab automation market valued at$5 billion in 2022,with projected CAGR of 6%-13%until 2028;dominated by automated liquid handling systems,with key established players like Tecan&Hamilton taking greatest market share;lab robotics also constitutes part of the

195、lab automation market,but is comparatively small at$290 millionA relatively new technology led by early-stage companies such as Emerald Cloud Lab&Strateos;labs currently focus on biotechnology&pharmaceutical industries for drug discovery&synthetic biologyChallengesTechnologies remain costly,especial

196、ly compared to the relatively low labor costs in academia;integrating novel automation technologies into existing workflows&infrastructure is a challenge,especially when these technologies are also not user-friendly&difficult to useData security&privacy concerns;a change in mindset would be required

197、 for more researchers to adopt this type of nontraditional experimentation methodMaturity TRL 7-9TRL 3-4Source:Arthur D.LittleFig 16 Enable technologies(contd)Micro-fluidicsLarge-scale fermentation technologiesEnable precise control over small-scale(microliter to picoliter)biochemical reactions for

198、diverse applications(e.g.,lab on a chip),achieving conditions unattainable by traditional methods;enable complex reactions with increased throughput&minimal wasteTraditionally involves microorganisms converting organic compounds,like sugars,into various useful products including bio-based chemicals,

199、fuels,flavors,fragrances,bioplastics&pharmaceuticals;now expanded to the fermentation of,for example,mammalian or microbial cells producing biologic compounds or even cells as products(e.g.,for artificial meat);unlike small-scale,PoC production in a lab,advanced fermentation technologies utilize opt

200、imized bioreactors,enabling cost-effective large-scale productionMarket is large&relatively mature,with various established players;market valued at$25-$29 billion in 2022 with a wide range for growth rate of 12%-23%CAGR;primarily used for medical purposes,specifically diagnostics(e.g.,rapid testing

201、),drug development&cell culturesWhile advanced genome engineering contributed to its development,there is still innovation&research in increasing the productivity or addressing scale-up challenges;technologies are quite mature,with numerous players already in the field,including large CDMOs(e.g.,Lon

202、za)&newer companies expanding into precision fermentation(e.g.,Perfect Day)Lack of standard test methods to validate manufacturing steps of devices&complex manufacturing,as they often require unique,heterogenous group of componentsIn non-pharma segments where fermentation competes with traditional c

203、hemical synthesis or lower-margin segments such as the food industry,topics are around cost-competitiveness;in other areas,such as alternative dairy,challenges are on generating the right quality;for pharmaceutical processes,topic centers on ability to produce more complex&potentially non-natural pr

204、oteinsin,for example,CHO cells;a digital twin is still not feasibleTRL 5-8TRL 7-934Blue Shift /REPORT 005Figure 17 shows the relative maturity of selected tools within each of the four SynBio workflow stages,based on ranking by our expert survey panel.Technology readiness levels(TRLs)indicate how cl

205、ose a tool is to proven,commercial adoption.Market landscapeThe majority of high-profile tool and technology players in SynBio are based in America(around half on a per-company basis).The remainder are divided approximately equally between Europe and Asia,with the rest of world currently having few

206、market entrants.The market is split between well over 500 SynBio start-ups and a much smaller number of more established players,with SynBio tool and technology players raising$10.3 billion in 2022.While most top-funded companies are currently headquartered in the US,the most dramatic growth is expe

207、cted in Asia,led by China.Many governments have targeted investments and support for SynBio.For example,the UK launched a SynBio program more than a decade ago,while the US,China,and Australia have created their own efforts more recently.Appendix 1 summarizes selected key players across the four too

208、l and technology development categories.Source:Arthur D.LittleFig 17 Relative maturity of selected tools within SynBio workflow Source:Arthur D.LittleFig 17 Relative maturity of selected tools within SynBio workflow TRL1-2ResearchTRL 3-4Lab PoCTRL 5-7Scale up&demoTRL 8-9Proven&commercialized/establi

209、shedDesign,model&simulateEngineer&buildTest&evaluate(analyze)Enable innovation&scaling Gene&protein design toolsNGS&high-speed real-time PCRSimulation tools for biological systemsAI&ML platformsManufactureof custom DNA sequencesDNA&gene delivery systemsGenome engineering toolsCloud labsAutomation te

210、chnologiesMicrofluidicsLarge-scale fermentationMass spectrometryHigh-content phenotypic imagingFlow cytometryFermentation technologiesRange of technology maturities“Center of gravity”of technology maturities Legend35Blue Shift /REPORT 005INTERLUDE#1 Evolving aesthetics Intersecting art&science in th

211、e language of cells 36Blue Shift /REPORT 005Our explorations in SynBio seek to reveal hidden processes in living matter through the manipulation of genes.We aim to transform these expressions in ways they can be experienced on a human scale.Consider an E.coli colony growing on a plate.Gradually,it s

212、preads and as conditions become more demanding it creates branches and intricate patterns.This phenomenon became the inspiration for our work Stress-o-stat(see first image in this section),which explored how genetic machinery responds to cellular stress.During dire conditions,cells produce the enzym

213、e catalase to neutralize damaging oxygen radicals.Analyzing the genetic mechanisms behind this response made it possible for us to replace the catalase gene with one producing a fluorescent protein.Our new genetic component,embedded in a genetic circuit and inserted into bacteria,caused the emission

214、 of an iridescent light during starvation.Using a drip system to regulate food release and a spiral condenser to visualize light changes,we observed the spiral light up during dire conditions and with changing nutrients we saw a slow oscillating light.Stress-o-stat aims to capture the poetic languag

215、e of“stress”in bacteria,with the luminescence telling a story of resilience and resourcefulness.To further expand on both method and metaphor,we explored how this could be done using solid media and time-lapse photography.As an additional play on the language of stress and signaling,KatEred(see seco

216、nd image)employed gene-producing,glowing-red fluorescent proteins.Observing growth patterns over time,a blushing red edge glowed as the colony spread across the plate,somewhat akin to tree rings telling the story of time and change.In our micro-environment,the colony creates a living visual story of

217、 struggles.37Blue Shift /REPORT 005SynBio can be a portal to see processes inside cells,but we can expand on this notation by tapping into other senses like smell.Banana Bacteria(see third image)adds an extra twist by subverting our expectations.It involved the use of a genetic program that could co

218、nvert an alcohol into banana oil,changing the typical off-putting smell of E.coli into a sweet-scented wonder reminiscent of bananas.It acts as a playful obfuscation that prompts us to introspect our preconceptions.However,genetically modified organisms are restricted typically to labs;exhibiting ou

219、tside these settings involves lengthy navigation of health and safety regulations as well as ethics review.Through our work,we have paved the way for the first legal exhibition in showing genetically modified organisms in the UK and beyond its borders.These works make invisible processes perceptible

220、 to humans.Yet,the absence of real-time interaction creates a barrier in how we experience these organisms and processes,often requiring us to add an interface like time-lapse to bridge the experience.Our initial real-time experiments used nanomagnetic particles,which allowed participants to control

221、 individual cells using an external magnet.Surprisingly,we found that magnetic bacteria occur naturally.These organisms swim along the Earths magnetic field to optimize their position in a microaerophilic gradient.Exposing these bacteria to a changing magnetic field causes their bodies to reorient a

222、nd,in doing so,scatter light.In liquid culture,the scattering can be observed as a visible shimmer resulting from blocking or passing light.This extraordinary phenomenon inspired our work Living Mirror(see fourth image).As a mirror,it draws on the idea of water as our original interface predating to

223、days screen-based technologies and references the myth of Narcissus,who tragically drowned while captivated by his reflection a reminder of how we continue to immerse ourselves in similar mirrors as we extend our identity into the virtual.To create the mirror,we used a camera to capture a persons im

224、age converting pixels into numerical values.This data activated individual magnetic coils,orchestrating bacteria to produce hundreds of light pulses that formed an image in real time.The work delves into the concept of“self”and how we are predominantly composed of nonhuman bacterial cells.It aims to

225、 capture a duality,both technically and conceptual,of how we navigate the intersection of digital and biological perceptions of self.C-LAB,an art-science collective founded by Howard Boland and Laura Cinti that combines scientific advancements in the biosciences,critical thinking,and future possibil

226、ities through hands-on science 38Blue Shift /REPORT 005Stress-o-stat Stress-o-stat is a living artwork that visually captures stress in bacteria as light.The installation combines scientific instruments,methods,and aesthetics to produce a real and experimental device.SynBio tends to postulate a mach

227、ine-like language onto the living,as something programmable.Paradoxically,it is the opposite of the digital;instead of the machines becoming life-like,it suggests life becoming machine-like.39Blue Shift /REPORT 005KatEred KatEred explores a living visualization of oxidative stress using a glowing-re

228、d fluorescent protein and through the use of time-lapse.The colony creates a blushing glow around its edges and creates an imprint of cellular stress over time.Red tends to signify an alert and has been used as“official”semantics in many apparatuses such as warning lights.While these factors play li

229、ttle in a biochemical role,they play with our perception as visual readers.40Blue Shift /REPORT 005Banana Bacteria Banana Bacteria is an olfactory work that explores the paradox of having the foul smell of bacteria exchanged with the sweet smell of banana.These bacteria have been genetically altered

230、 by removing a gene responsible for the foul smell commonly found in bacteria and adding a genetic design that enables bacteria to synthetically produce banana oil.41Blue Shift /REPORT 005Living Mirror Living Mirror is a bio-computational imaging system where magnetic bacteria scatter light under a

231、changing magnetic field.This phenomenon was used to create a bio-computational system containing bacteria and individually controlled magnetic coils to recreate patterns and potentially real-time images of people.42Blue Shift /REPORT 005“If you cant compute it,you dont understand it!.”John von Neuma

232、nn,physicist/engineerBlue Shift /REPORT 0054344CHAPTER44345THE APPLICATIONS&INDUSTRY LANDSCAPE3The applications&industry landscapeSynBio underpins a diverse range of applications across many industries,led by healthcare and life sciences and food and agriculture.The application landscape demonstrate

233、s the enormous scope of SynBio.For example,it can be used to create vaccines,improve crops,generate biofuels,and enable DNA-based data storage.Consequently,there are widely varying levels of maturity among applications,ranging from early stage through to full commercialization.Blue Shift /REPORT 005

234、46Identifying SynBio opportunitiesOur 2023 global expert survey explored industries that would be most impacted by SynBio in the next five to 10 years(see Figure 18).About a quarter of respondents identified healthcare and life sciences as the sector that will see the greatest applicability of SynBi

235、o,followed by food and agriculture(21%),and then industrial,manufacturing,chemicals,and materials(18%).Application maturity Mapping selected SynBio applications against the Gartner hype cycle further demonstrates both their range and the diversity of their maturity levels(see Figure 19):-Healthcare

236、and life sciences.Various subsectors in healthcare are at differing points on the curve.For example,widely used monoclonal antibodies as a treatment option are at the peak of productivity,whereas newer therapeutic modalities like gene therapies are considered to be at the peak of inflated expectatio

237、ns.-Food and agriculture.This sector is approaching the peak of inflated expectations,as it is maturing with products that are commercially available,yet market uptake is still relatively limited.Newer technologies that use SynBio techniques are on the brink of commercialization and those that addre

238、ss current sustainability challenges around food production(e.g.,cell agriculture for cultured meat)are at the technology trigger stage.Fig 18 Which industries will be most impacted by SynBio in the next five to 10 years?Source:Arthur D.LittleSource:Arthur D.LittleFig 18 Which industries will be mos

239、t impacted by SynBio in the next five to 10 years?Healthcare&life sciences26%Food&agriculture21%Consumer goods17%Energy11%Industrial,manufacturing,chemicals&materials 18%IT&tech7%47Blue Shift /REPORT 005-Industrial,manufacturing,chemicals,and materials.This segment is approaching the peak of inflate

240、d expectations,as demand for novel enzymes for many end-use industries continues to grow.Commodity chemicals are also at the peak of an inflated expectations phase,while partnerships between industry players(e.g.,Unilever)and SynBio companies continue to form.-Consumer products.Approaching the slope

241、 of enlightenment,this segment is maturing with some commercially available products(e.g.,fragrances,plant-based leather alternatives).With sustainability at the forefront of consumers minds,the use of SynBio to generate consumer products will continue to grow.-Energy.This sector is at the trough of

242、 disillusionment,as biofuels and bio batteries continue to be slow to overcome economic and technical barriers.However,next-generation biofuels produced from waste materials and other co-products will still have applications in,for example,heavy-duty transport,such as aviation and shipping,that are

243、difficult or impossible to electrify.-IT and technology.Just beyond the technology trigger phase,major players are starting to investigate the adoption of SynBio tools and techniques like DNA data storage.This is evident through the growing number of partnerships between SynBio companies and tech pl

244、ayers(e.g.,Twist and Microsoft;Illumina and Dell).Fig 19 Selected SynBio applications mapped to Gartner hype cycle Source:Arthur D.Little,Nasdaq,SynBioBeta,Calvin Schmidt Synthetic Biology IndexSource:Arthur D.Little,Nasdaq,SynBioBeta,Calvin Schmidt Synthetic Biology IndexFig 19 Selected SynBio appl

245、ications mapped to Gartner hype cycle TimeExpectationPeak of productivityTrough of disillusionmentPeak of inflated expectationsSlope of enlightenmentTechnology triggerGene therapy&cell-based therapiesMonoclonal antibodiesPlant-based meat alternativesDNA data storagePlant-based leather alternativesFr

246、agrances developed using synthetic biologymRNA vaccinesNext-generation biofuelsBio-batteriesCellular agricultureEnergyIT&techFood&agricultureHealthcare&life sciencesHealthcare&life sciencesHealthcare&life sciencesFood&agricultureEnergyConsumer productsConsumer productsPossible failure or declineNove

247、l enzymes,commodity chemicalsIndustrial,manufacturing,chemicals,materials48Blue Shift /REPORT 005Key areas for growthComparing growth and maturity provides an indication of the significance of each of the key application sectors today(see Figure 20).As Figure 20 illustrates,healthcare and life scien

248、ces is the most mature and largest market,with one of the highest growth rates.Food and agriculture is next,although there is still extensive tech development in this segment at low TRLs.Industrial/manufacturing/chemical/materials,consumer goods,and energy are also growing,although barriers toward c

249、ommercialization are higher,with IT and tech being the most embryonic.However,if DNA-based storage could be commercialized,this could become a huge market.The remainder of this chapter takes an in-depth look at each of these markets,including potential applications,opportunities,and challenges.Healt

250、hcare&life sciencesMotivations for SynBio applications in the healthcare and life sciences sector are strong.Key catalysts include:-Rising incidence of chronic and debilitating disorders(e.g.,cancer).The aging population and resulting rise in chronic diseases increases the need for more specialized

251、treatments.-Shift toward personalized/precision medicine.The movement toward more targeted,individualized treatments/therapeutics will increase SynBio use,as it enables fine-tuning of organisms to perform specific/dynamic functions.-Limitations of current treatments.SynBio can improve both efficacy

252、and safety of current treatments,as well as satisfy the need for a new treatment method and mechanism.Fig 20 Identifying key SynBio markets Source:Arthur D.LittleSource:Arthur D.LittleFig 20 Identifying key SynBio markets High(20%CAGR)Typical technology maturityFood&agricultureHealthcare&life scienc

253、esIndustrial,manu.,chem.,materials Low(10%CAGR)Low(TRL1-5)High(TRL6-9)Consumer goodsEnergy Size of bubble indicates relative market sizeIndicates range of SynBio TRLs across sectorIT&tech?Forecast growth to 203049Blue Shift /REPORT 005However,success will require the sector to overcome existing chal

254、lenges in four key areas:1.Regulations.Strict regulations regarding drug development and a relatively untested regulatory environment make the process lengthy and costly.2.Ethical limitations.Public hesitancy and debates regarding ethics of modifying the genome hinder SynBio expansion.3.Limited tech

255、nological capacity(e.g.,data streams and computer capacity).Technological capacity limitations hamper the ability to actualize all possible SynBio developments.4.Complexity of large-scale production and manufacturing of cell therapies.The complexity around manufacturing cell therapies and the limita

256、tions of large-scale production complicate the process of taking a SynBio concept from lab to commercial scale.Application areas(non-exhaustive)Tissue engineeringSynBio enables the creation of multicellular structures for regenerative medicine,drug testing,and beyond,including tissues and organs usi

257、ng cells and structural components to mimic the morphology and function of native tissues.For example,gene therapy,advanced biologics,and small molecules are being studied to stimulate the regeneration of damaged heart cells.SynBio can be used to generate tissues that can then be transplanted.As an

258、example,cultured epidermal autografts are being used as a permanent skin replacement for the treatment of patients with serous burn injuries.The tissue engineering market is already large and well established at around$15 billion globally in 2022,with growth of more than 15%CAGR to 2030.Most SynBio

259、applications are still at foundational stages,with key players like Integra LifeSciences and C.R.Bard(acquired by BD in 2017)still focusing mainly on conventional technologies.Start-ups such as Organovo focus on new 3D biomaterial printing.Medical devices&implants Integrating SynBio into wearables c

260、ould expand opportunities for noninvasive monitoring of physiological status,disease states,and exposure to pathogens or toxins to practically enable biosensors.However,sustaining living organisms in medical devices for extended periods remains a challenge.Potential application examples include new

261、wearable or implanted medical devices for health monitoring and control.Demonstrating this trend,a prototype face mask with a lyophilized(i.e.,freeze-dried)CRISPR sensor has been developed for wearable noninvasive detection of SARS-CoV-2 at room temperature.50Blue Shift /REPORT 005Most SynBio applic

262、ations are still at foundational stages.VaccinesVaccines are commonly prepared from an inactivated or weakened form of the causative agent or from its constituents.SynBio facilitates shorter development cycles through alternative technologies,such as nucleic acid vaccines(e.g.,mRNA),viral vector vac

263、cines,or recombinant vaccines(e.g.,SHINGRIX).For example,synthetic RNA platforms allow for rapid,scalable,and cell-free manufacturing of prophylactic and therapeutic vaccines.The Pfizer-BioNTech COVID-19 RNA vaccine was the first to be approved for humans.Moderna and BioNTech are examples of key pla

264、yers that used synthetic messenger RNA to protect against COVID-19.Stem cell therapiesStem cells serve as the raw material from which all specialized cells are derived,capable of generating healthy replacements for cells impacted by disease(regenerative medicine).Achieving this transformative proces

265、s is made possible through genetic reprogramming techniques such as CRISPR.For example,stem cells can be manipulated into heart muscle cells,which can then be injected into the heart muscle of a patient with heart disease.The transplanted cells would then aid in repairing the injured muscle.The glob

266、al stem cell therapy market was valued at$10 billion to$12 billion in 2022 and is predicted to grow at a 10%-15%CAGR for the next 10 years.An influx of interest and funding has resulted in both emerging players,like bluebird bio and BlueRock Therapeutics,and more established players,like Mesoblast a

267、nd Osiris Therapeutics,coexisting in the expanding market.Cell therapiesSynBio enables the development of therapies based on bioengineered cells.In these currently highly personalized treatments,cells are becoming the treatment modality.Among the first treatments in this space was Kite Pharmas CAR T

268、-cell therapy,but there are many more in development to treat a variety of disorders and diseases.For example,CAR T-cells have successfully treated blood tumors such as large B-cell lymphoma and also promise a new scenario of therapeutic interventions for solid tumors.The genetically modified cell t

269、herapy market is projected to grow rapidly from$2.7 billion in 2022 to$32.3 billion in 2029 at a CAGR of 42%.Main players in the space include large pharma players such as Bristol Myers Squibb and Gilead,which have expanded their cell therapy capabilities through acquisitions of Juno/Celgene and Kit

270、e Pharma,respectively.However,there are several smaller biotech players harnessing this technology with assets in the early development phases,including Allogene and Ixaka(formerly Rexgenero).Gene therapiesSynBio has enabled scientists to cure diseases by correcting the underlying genetic defects th

271、rough genomic editing(e.g.,CRISPR)or introduction through a vector(usually a viral vector).Alternatively,synthetic oligonucleotides can be used to modify the genetic response,with RNAi currently being the most prominent technology.51Blue Shift /REPORT 005An influx of interest and funding has resulte

272、d in both emerging and more established players.For example,vector-based gene therapies have been approved for both hemophilia A and B.In both cases,viral vectors are used to deliver the correct gene and potentially cure the patients through a single treatment,although long-term data is not yet avai

273、lable.The gene therapy market is projected to grow rapidly at a CAGR of 20%from$7.5 billion in 2022 to$30 billion in 2030.Examples of key established players are large pharma players such as Novartis as well as more niche players like Vertex.The approved gene therapies are currently centered on hema

274、tological genetic diseases,such as hemophilia and severe sickle cell anemia,but also include degenerative inherited diseases.Gene therapies for some larger indication areas,such as type 1 diabetes,are also in development.Bio-machine interfaces SynBio technology could provide solutions for developing

275、 effective bio-human-machine and neuro-machine interfaces.For example,it has been demonstrated that closed-loop brain-machine interface(BMI)technology can modulate sensory-affective experiences in rats,illustrating how a BMI approach could be used for pain control as an alternative to drugs.Numerous

276、 healthcare applications exist,such as restoring physical functions and controlling symptoms.There are also applications in education and entertainment,where BMI technology could be used,for example,to control avatars and objects,contributing to a more immersive gaming experience.Maturity timelineIn

277、 the future,SynBio is expected to lead to more sophisticated treatments,greater safety from more diseases,and new applications for existing conditions,such as neurological and genetic ailments.Figure 21 outlines the maturity timeline across the healthcare and life sciences sector.Fig 21 Maturity tim

278、eline for SynBio applications in healthcare and life sciences Source:Arthur D.LittleSource:Arthur D.LittleFig 21 Maturity timeline for SynBio applications in healthcare and life sciences Faster,real-time diagnosis&reporting Improved safety of treatments by enabling more targeted cell therapies with

279、lesser side effectsMulti-targeting treatment&vaccines,which will expand the scope of addressable diseasesAdvanced drug discovery by leveraging synthetic gene circuits in synthetic biology(e.g.,in&beyond antimicrobial resistance)5-10 yearsVaccine&drug developmentDiagnosticsImmunology Tissue engineeri

280、ng Precision/personalized medicines&therapiesNow Changes in how we handle genetic&neurological diseases based on ability to map neural pathways,enabled by implantable technologies&devices Biomolecular systems that can cross the blood-brain barrier&brain implants to restore functionDecrease of trial-

281、and-error nature of clinical trials due to increased predictability&rational engineering Predictive genetic engineering for multicellular organisms(e.g.,animal&human organs)Wearable&noninvasive biosensors10+years 52Blue Shift /REPORT 005Food&agricultureFeeding a growing global population while copin

282、g with the immediate impacts of climate change is a critical challenge for the world for several reasons:-Sustainability and accompanying policy and regulatory changes.Demand is growing for SynBio solutions due to their ability to provide results while protecting the environment and maintaining or i

283、mproving soil fertility.-Population growth.Population growth has been projected to require improvements in productivity/yield by 60%-80%up to 2050,increasing demand for SynBio improvements.Initiatives are increasingly being driven by governments(e.g.,Singapores 30 by 30 food security and sustainabil

284、ity plan).-Plateauing yields with current improvements.Limitations in current farming improvements,such as fertilizers and greenhouses,are making the industry look to other more effective options for higher yields.Successful SynBio adoption will require the sector to overcome existing challenges in

285、three key areas:1.Regulation.Elements of the emerging regulatory environment remain untested,creating compliance challenges.2.Public perception.Consumers,especially in Europe,have negative views of existing genetically modified food and technologies(e.g.,gene/genome editing).This negatively impacts

286、demand for SynBio-derived products and potential market growth.3.Risk aversion.SynBio adoption involves disruptive change within the market.Larger companies with established systems,in particular,are reluctant to change how they operate,holding back adoption.Application areas(non-exhaustive)Crop dom

287、estication&breedingSynBio enables metabolic pathways,genetic circuits,and plant architectures to be engineered for agricultural plants,enhancing their suitability to human needs,such as around taste/flavor,color,yield,storage,productivity,amino acid production,ability to fix nitrogen,and disease res

288、istance.SynBio offers a major enabler to reduce the time required for crop breeding cycles by making use of existing genomic data sets,as well as deploying other toolsets to expedite the breeding cycle which,for some crop varieties,may take five to seven years.For example,Pivot Bio used an engineere

289、d bacterium to create a biological nitrogen fertilizer for corn,reducing the need for chemical fertilizer while increasing yield.The crop-breeding market is expected to reach over$30 billion by 2029.Major players,such as Benson Hill and Apeel,are being joined by smaller companies like Tropic Bioscie

290、nces.53Blue Shift /REPORT 005Initiatives are increasingly being driven by governments.Precision agriculture SynBio can improve the physical properties of soil in a variety of ways;for example,through improving soil microbiomes via microbial fertilizers,enabling soil remediation,and developing natura

291、l pesticides,as well as helping to diagnose potential pests and diseases in soil and water.This type of improvement includes the use of novel bio-fungicidal seed treatments to control soil-borne fungal pathogens that cause seed rot,damping-off,root rot,and seedling blights while minimizing environme

292、ntal impact.The global precision agriculture market reached a value of around$6.7 billion in 2021.Governments across the globe have undertaken several initiatives to encourage the uptake of modern agricultural techniques to enhance crop yield and productivity.Syngenta Group and Bayer Crop Science ar

293、e leaders in precision agriculture.However,as the need for precision agriculture continues to grow,there are several start-ups and smaller players entering this space,such as Pivot Bio,Concentric,and Robigo.Designer synthetic&bio-based foodSynBio can be applied to engineer food not produced in natur

294、al soil or obtained from animals(e.g.,microbial nutritional protein).Such food is produced artificially in both laboratory and industrial conditions,using a culture or growth medium.For example,in 2016,Impossible Foods launched the Impossible Burger,a vegan alternative to a beef hamburger.The proces

295、s uses genetically engineered yeast to produce the heme protein needed to make the food look and taste more like meat.The global synthetic food and ingredients market is estimated at around$12 billion to$13 billion in 2022.Impossible Foods and Beyond Meat currently dominate the plant-based meat mark

296、et.The increasing number of new plant-based food start-ups and the expansion of the food service industry will further drive growth.Start-ups providing animal-free dairy proteins,including ImaginDairy and Perfect Day,are also rising in popularity.Bioremediation,biosequestration,biosensorsSynBio can

297、be used to create genetic-engineered microorganisms and microbial consortia to improve the efficiency of bioremediation,especially in heavily contaminated or difficult-to-access environments.An example of this is the work of UK-based CustoMem,which uses SynBio to create a granular material that attr

298、acts and sticks to micropollutants,such as pesticides,pharmaceuticals,and certain chemicals in wastewater.The global bioremediation market is estimated at around$13 billion to$14 billion in 2022.Growth will be driven by increasing environmental awareness as well as regulatory demands,with bio altern

299、atives perceived as more natural,as well as being cost-effective in many cases.The market is fairly fragmented,but major players include Xylem,Drylet,Aquatech,and others.Governments across the globe have undertaken several initiatives.54Blue Shift /REPORT 005Maturity timeline Moving forward,we expec

300、t SynBio adoption to lead to further developments in crop technologies,food engineering,and environmental remediation approaches across the food and agriculture sector(see Figure 22).Industrial,manufacturing,chemicals&materialsThe need to decarbonize,reduce waste,and become more sustainable is incre

301、asingly impacting industrial companies and their operations.Key drivers include:-Sustainability needs and accompanying policy changes.Increased global awareness of environmental issues will likely result in further regulations restricting fossil fuel manufacture.-Technological advances enabling new

302、innovations.New and evolving technology will reduce the cost and complexity of applying SynBio developments.-Waste reduction from large-scale production.SynBio technologies can both improve and replace current manufacturing processes that produce large amounts of waste.-Rare earth and mined material

303、s supply constraints and security.The transition to net zero will require huge increases in mined raw materials,especially metals.This will increase further the need for more sustainable production processes.Fig 22 Maturity timeline for SynBio applications in food and agriculture Source:Arthur D.Lit

304、tleSource:Arthur D.LittleFig 22 Maturity timeline for SynBio applications in food and agriculture Crop gene editing to endow foreign but natural functionsFaster-growing crops,more resilient to environmental stress,higher nutritional content&diversity Increasing variations&use of biofertilizers3D pri

305、nting of food in near-true likeness in substance&formGenetically engineered organism(GEO)animalsEnhancing existing functions in crops to improve yields&create crops that are more flavorsome,colorful&resistant to pests,diseases&changing environmental conditionsCellular agriculture;production of groun

306、d meat with a focus on tasting the same as meat from animalsAiding precision agriculture in improving crop yields&assisting decisions using high-tech sensor&analysis toolsEndowment of functions not yet existing in nature to mass production crops with significant ecological upsidesCapture CO2 more ef

307、ficiently,require less nitrogen(and thereby,fertilizers)&less water,among other propertiesXenobots in agriculture to help apply synthetic pesticides&fertilizers5-10 yearsNow 10+years 55Blue Shift /REPORT 005However,major challenges to SynBio adoption remain in three key areas:1.Cost.Though more sust

308、ainable,the high cost and greater energy consumption of SynBio processes at scale are major barriers to adoption.2.Risk aversion.Players with large-scale,established infrastructures(e.g.,chemicals industry)and profitable systems are hesitant to adopt SynBio alternatives,due to the high costs and ris

309、ks inherent in such a major transformation.3.Collaboration.Many SynBio solutions require the formation of new ecosystems,creating nontraditional partnerships;for example,between materials companies,technology providers,manufacturers,consumers,and environmental companies.Application areas(non-exhaust

310、ive)Bio-based specialty productsBio-based specialty products can be created via new production pathways where microorganisms generate a wide variety of chemicals.While many processes are already established,SynBio offers the potential to improve them.For example,the hyaline family of clear,flexible

311、films are used for flexible electronics(e.g.,foldable smartphones and wearable electronics).The bio-based specialty products sector is primarily dominated by larger players,including BASF,Toray Industries,and Novamont.These companies have significant financial backing and partnerships already in pla

312、ce.Companies like Toray have developed plant-based synthetic fibers,while Novamont has focused on the development of biodegradable bioplastics by applying SynBio techniques.Sustainable production/manufacturingUsing microorganism strains engineered to produce defined outputs(e.g.,production of small

313、molecules of high value)helps reduce reliance on petrol-based and even plant-based chemicals and processes.For example,engineered microbes and biotechnological copper-recovery applications are already being applied in copper mining,including for bioleaching,accumulation,and recycling.The market for

314、sustainable production/manufacturing is extremely broad and diverse,including,for example,pharmaceuticals,commodity chemicals and materials,consumer goods,and bioremediation,all of which are covered elsewhere in this Report.Commodity chemicals&materialsCommodity chemicals can now be engineered and p

315、roduced from microbes and more renewable materials(e.g.,value-added chemicals can be synthesized from flue off-gases).As one example,Biomason uses bioengineered bacteria to“grow”bricks.The company claims these“Biocement”bricks are as strong as traditional cement and are made on-site using local mate

316、rials.Major challenges to SynBio adoption remain.56Blue Shift /REPORT 005Biotech companies such as Ginkgo Bioworks and Genomatica have focused on the commodity chemicals and materials sector,with Gingko valued at$15 billion in 2021.Genomatica has developed partnerships with Unilever to develop alter

317、natives to palm oil and fossil fuels.The company has also partnered with global chemical company Asahi Kasei to commercialize renewably sourced nylon.Enzyme productionSynBio techniques such as DNA synthesis and heterologous expression can be used to produce novel enzymes with improved properties.For

318、 example,Arzeda has developed Intelligent Protein Design Technology,which combines physics-based protein design and AI to create new designer proteins and enzymes,which it claims to be more efficient and less risky than conventional approaches.The rising demand for novel enzymes is attributed to gro

319、wing product demand in various end-use industries(e.g.,detergents for industrial applications).Established players like Novozymes and BASF have several partnerships in place with companies across consumer care and biopharmaceuticals.Additionally,there are many less mature players,including Arzeda,th

320、at have received limited funding but have developed significant partnerships with companies,including Unilever,Amyris,and BP.Maturity timeline In the future,we expect increased penetration of SynBio technologies into industry and manufacturing,provided that the economic challenges can be solved(see

321、Figure 23).Fig 23 Maturity timeline for SynBio applications in industrial,manufacturing,chemicals,and materials Source:Arthur D.LittleSource:Arthur D.LittleFig 23 Maturity timeline for SynBio applications in industrial,manufacturing,chemicals,and materials Increased use&production of bioplastics,bio

322、-lubricants&bioproduction of dyesLarge-scale tuning of biological pathways and/or modification of enzymes to create modified materials specific to use cases while utilizing less environmentally harmful materials as substrates5-10 yearsUsed to produce a wide range of products,including chemicals,enzy

323、mes&proteins more efficiently&sustainablyBio-based replacements are already being adopted for conventional materials(e.g.,biological materials to replace cement)Now New biodegradable materials(e.g.,bioengineered inorganics/composites)Reliance on bio-based production of materials,sustainable syntheti

324、c routes replacing current production methodsCircular bioeconomy established with cells that function with more sustainable feedstocks to create new materials with new properties,recycle to extract desired materials&break down harmful material10+years 57Blue Shift /REPORT 005Consumer goodsSustainabi

325、lity and personalization,particularly in the luxury goods and fashion sectors,are strong drivers,in addition to the following:-Sustainability and accompanying policy changes.SynBio solutions typically offer sustainability benefits for governments looking to meet sustainability goals.-Consumer awaren

326、ess.There is increasing consumer awareness and demand for more sustainable production and products.-Personalization.There is a growing market for designer,personalized,and high-end consumer products.Personalization is a major trend in luxury consumer goods.-Rising energy prices.High energy prices ar

327、e driving manufacturers to seek alternative processes and less energy-intensive production processes,perhaps even at the expense of time-to-product.Successful SynBio adoption will require the sector to overcome existing challenges in three key areas:1.Scale.Many consumer products using SynBio can on

328、ly be produced on a small scale.The cost and time-to-market for these products may therefore be very high,especially given that some involve relatively novel technologies.2.Cost.The cost-effectiveness and established infrastructure for fossil fuels in commercial production can make changing to SynBi

329、o economically unattractive,particularly as it is a less mature technology.3.Public perception.Consumers may be wary of SynBio products,particularly in areas where“natural”products are seen as premium,or where humans are in close physical contact with the product(e.g.,cosmetics).Application areas(no

330、n-exhaustive)Flavors&fragrancesBy applying biosynthesis and precision fermentation,SynBio creates alternative pathways for molecules traditionally sourced from plant or animal materials.For example,Evolva applies precision fermentation to develop flavors and fragrances,such as nootkatone,valencene,v

331、anillin,and L-arabinose.The global fragrances market has been valued at$59 billion in 2023.Both Amyris and Conagen are mature players in the SynBio-based fragrances space.Amyris has had several partnerships to develop bio-based fragrances,including with Maison Francis Kurkdjian.Conagen is a global l

332、eader in developing natural fragrances and its vertical integration has enabled it to rapidly commercialize fragrances.Successful SynBio adoption will require the sector to overcome existing challenges.58Blue Shift /REPORT 005Consumer materials,textiles,fabricsSynBio provides the ability to create m

333、ore sustainable(carbon-negative)textile materials,both improving existing textiles and creating novel,animal-free materials.For example,Hide Biotech produces a leather-like material by transforming food industry waste into a customizable collagen-based leather substitute.The global vegan fashion market,which includes any apparel not using animal products including non-synthetic materials,was value