漢贊迪&比鄰星創投：2023智能技術在合成生物學中的應用白皮書(47頁）.pdf

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1、?割?研 BCC?research?研?2021?95?2026?332?2021-2026?撐?(CAGR)?28.4%?篩?封?覆?割?撐練?割?務?模?-?-?-?DBTL?封?的?封?2?1?展?.?3 1.1?.3 1.1.1?.3 1.1.2 DBTL?.4 1.1.3?.5 1.1.4?.8 1.2?.9 1.2.1 篩?.9 1.2.2?.10 1.3?.13 1.4?Ginkgo?Bioworks?.15 2?展?.?18 2.1?-?DBTL?.18 2.2?-?.19 2.2.1?.20 2.2.2 SDLs?-?.26 2.3?-?.27 2.3.1?Biofoundr

2、y?TALENs.29 2.3.2?BioAutomata.31 2.4?-?.33 2.4.1?.34 2.4.2?.35 2.4.3?.37 2.4.4 iBioFoundry?務?.38 3?展?.?40 3.1?.40 3.2 SDLs?-?.41 3.3?SDLs?.43 4?.?44?3?1?展?1.1?1.1.1?Synthetic?Biology?去?封?導?去?勃?DNA?封?1953?2003?研?National?Institutes?of?Health,?NIH?National?Genome?Research?Institute?覆?撐?撐練?DNA?封?確?20?2

3、1?告?去?4?1.1.2 DBTL?撐練?撐練?-?-?-?DBTL?DBTL?撐?1.?-?-?-?覆?1.?Design?DBTL?去?務?DNA?務?去?2.?Build?DNA?DNA?封?務?割?的?割?研 DNA?DNA?封?BioBrick?BglBricks?In-Fusion?Gateway?Golden?Gate?Start-Stop?DNA?(Oligonucleotides?linkers?mediated?DNA?assembly?OLMA)?去?(Zinc?finger?nucleases?ZFN)?去?TALEN?封?去 CRISPR-Cas?CRISPR-Ca

4、s?5?CRISPR-Cas9?CRISPR-Cas12a?(Cpf1)?務?割?務?3.?Test?盟?RBS?去?去?封?DBTL?DBTL?研?25?務?(?)?300?600?/d?撐練?100?/d?90%?4.?Learning?DBTL 務?-RNA-?-去?-?割?-?去?覆?研?研?研?告?研?研?去?研?研?DBTL?割?1.1.3?夠?/?/?6?導?撐練?去?DBTL?DNA?DNA?DNA?去?1.DNA?DNA?封?1)?務?2)?3)?Sanger?去?DNA?去?2.DNA?DNA?研?21?DNA?封?2.?DNA?務?DNA?DNA?DNA?3.?3?ZFN

5、?7?TALEN?CRISPR/Cas?DNA?去?去 CRISPR/Cas9?1)?2)?ZFN?TALEN?3)CRISPR/Cas9?ZFN?TALEN?CRISPR-Cas?Cas?CRISPR?務?CRISPR-Cas?3.?CRISPR?封?Strategies?to?overcome?the?main?challenges?of?the?use?of?CRISPR/Cas9?as?a?replacement?for?cancer?therapy?4.DNA?DNA?DNA?DNA?DNA?DNA?DNA?ligase?chain?reaction,?LCR?polymerase?

6、cycling?assembly,?PCA?群?DNA?務?DNA?封?8?1.1.4?告?封?1910?Stephane?Leduc?synthetic?biology?告?2000?封?Nature?去?封?割?DNA?去?封?封?割?10?10?2003?去?務?去?務?2004?-?2007?的?告?2008?-?2013?去?Amyris?2014?-?-?-?研?4.?封?去?9?務?告封?封?封?割?研?資?割?封?1.2?1.2.1 篩?裂?封?篩?封?務?/?封?篩?封?篩?篩?封?務?封?封?夠?篩?封?封?篩?2012?2016?封?夠?封?封?2019?3?封?去?去?

7、封?篩?L-?6-APA?篩?973?863?封?夠?2022?5?封?封?封?夠?封?封?篩?封?10?5.?封?1.2.2?2021?Zymergen?Ginkgo?IPO?盡?2021?研 Synbiobeta?研?2009-2020?盡?215?2021?180?12?80%?6.?2009-2021?Synbiobeta?11?2018?割?的?研?研?2022?割?2022?模?54?2021?2023?模?103?300?模?去?2022?1?模?8.7?B3?2023?2?模?4?B4?盡?B?19?送?封?務?A?A?2?模?務?割?告?盡封?7.?2023?去?2023/7

8、/11?A?2023/7/06?Pre-A?2023/6/30?2023/6/25?B?2?務?FDCA?CellX?2023/6/16?A+?12?2023/6/06?A+?-?2023/5/30?+?-?2023/4/26?A+?2023/4/25?Pre-A?2023/4/20?B1?Green?Future?研?2023/3/21?Pre-A?2023/3/21?A?-?2023/3/18?Pre-A?2023/3/8?+?-?2023/2/20?B?AI?2023/02/14?B4?4?務?務?-?務?2023/02/02?A+?3.95?務?PHA?務?56?2023/01/16?

9、Pre-A?-?13?1.3?盡?DNA&RNA?務?盡?封?盡?盡?盡?盡?封?務?DNA?封?研?務?Twist?Biosciences?研?DNA?Desktop?Genetics?CRISPR?務?盡?務?盡?封?盡?封?Ginkgo?Bioworks?MetaMixis?盡?封?封?盡?盡?盡?盡?割?去?務?1.?Poseida?Therapeutics?Antheia?2.?Lygos?務?Green?Biologics?3.?務?14?LanzaTech?4.?Agrivida?Plant?Sensory?Systems?5.?Modern?Meadow?6.?Ava?Wine

10、ry?撐?務?撐?8.?CB?Insights?模?務?去?空?務?研?封?封?去?15?務?確?去?1.4?Ginkgo?Bioworks?Ginkgo?Bioworks?盡?2008?MIT?Tom?Knight?MIT?Jason?Kelly?Reshma?Shetty?Barry?Canton?Austin?Che?4?2021?9?Ginkgo?Bioworks?150?Ginkgo?Bioworks?務?盡?盡?Foundry?去?Codebase?1?研?研?2?Ginkgo?Bioworks?2017?9?Ginkgo?Bioworks?Bayer?盡Joyn?Bio?封?20

11、21?4?Ginkgo?Bioworks?Corteva?Agriscience?封?2016?10?Ginkgo?Bioworks?Cargill?ADM?封?2018?11?Ginkgo?Bioworks?盡 Glycosyn?封?HMO?2019?2?Ginkgo?Bioworks?9000?Motif?Food?Works?去?封?割?去?2018?9?Gingko?Bioworks?盡 Cronos?Group?1.22?夠?/?16?2019?6?Gingko?Bioworks?Roche?1600?封?2019?6?Ginkgo?Bioworks?Synlogic?8000?封?

12、2020?Ginkgo?Bioworks?Concentric?夠?COVID-19?2020?10?Ginkgo?Bioworks?4000?Allonnia?封?務?群?9.?Ginkgo?Bioworks?Ginkgo?Bioworks?Ginkgo?Bioworks?2023?2.75?務?1.75?2023?1?Ginkgo?2023?Foundry?100?2023?Q1?13?Ginkgo?1.?研?Foundry?DNA?模?2.?研?研?Ginkgo?去?(Codebase)?研?Codebase?撐?Foundry?去?Codebase?17?Ginkgo?10.?Gink

13、go?Bioworks?Foundry?+?Codebase?Ginkgo?Bioworks?18?2?展?2.1?-?DBTL?封?去CRISPR/Cas9?DNA?DNA?種?研?7?去?告?割?DNA?告?DNA?務?割?務?1-100?的?100-10?封?割?割?務?研?封?研?研?去?割?封?研?務?封?告?割?研?割?研?研?研?DBTL?19?研?DNA?研?務?-?-?-?DBTL?1?務?11.?割?-?-?-?(DBTL)?研?夠?研務?去?務?UIUC?2.2?-?務?割?去?研務?研?務?研?務?20?2.2.1?Directed?Evolution?DE?務?Mac

14、hine?Learning?ML?務?撐練?研?覆?1.?2.?3.?研?4.?研?5.?去?12.?覆?Cell?Systems?A.?確?MLDE?割?21?割?EVmutation?DeepSequence?MSA?研?研?割?ESM?ProtTrans?13.?研?研?匹?Cell?Systems?B.?封?研?撐練?務?去?務?去?22?14.?研?撐練?Cell?Systems?研?研?100?N?N?割?N-?務?封?NLP?Doc2Vec?mLSTM?transformer?務?NLP?研?割?NLP?封?NLP?AlphaFold?23?RoseTTAFold?ESMFold

15、?研?N?C.?MLDE?割?20?割?模?確?務?20?告?MLDE?15.?確?/?確?Cell?Systems?24?MLDE?告?研務?D.?務?務割?尺?尺?確?務?告?E.?封?務?模?告導撐?研?撐?務?務?iBioFAB?封?DNA?iBioFAB?BioAutomata?務?25?16.?MLDE?Cell?Systems?17.?務?務?Cell?Systems?SDLs?Self-Driving?Labs?Autonomous?Experimentation?SDLs?務?告?26?2.2.2 SDLs?-?SDLs?研?研?18.?SDLs?ScienceDirect?

16、務?SDLs?DNA?去?去?務?去?AI?空?空?研?割?去?AI?空?務?SDLs?Self-driving?labs?務?模?夠?研?割?告?模?封?模?SDLs?-?-?-?27?19.?SDLs?ScienceDirect?SDLs?3?務?0?研?1?撐?2?研?3?-?-?-?SDLs?研?4?研?Adam?Eve?夠?SDLs?5?SDLs?2.3?-?務?務?PCR?28?務?匹?匹?BioFoundry?篩?3?務?篩?6?務?資?千?務?務?封?Amyris?盡?Ginkgo?Bioworks?盡?Zymergen?盡?Transcriptic?盡?割?務?-?-?-?2

17、0.?務?夠?DARPA?Living?Foundries?夠?夠?2011?5?29?4?封?1?1?DNA?DNA?10?20?1/4?7.5?夠?告?確?去?2.3.1?Biofoundry?TALENs?TALENs?TALENs?DNA?TALENs?千?告?割?TALENs?Huimin?Zhao?P2A?TALENs?封?務?TALENs?96.2%?TALENs?TALENs?務?TALENs?Huimin?Zhao?模?TALENs?TALENs?Huimin?Zhao?iBioFAB?模?iBioFAB?20?割?DNA?21?a?b?封?21?c?30?21.?iBioF

18、AB?a.?b.?iBioFAB?iBioFAB?5?務?c.?iBioFAB?GUI 務?封?iScheduler?GUI?割?ACS?Synthetic?Biology?iBioFAB?DNA?務?Golden?Gate?DNA?Huimin?Zhao?封?Script?Generator?DNA?DNA?iBioFAB?撐練?iBioFAB?iBioFAB?TALENs?iBioFAB?尺?DBTL?務?尺?46?iBioFAB?務?Golden?Gate?撐務?尺?確?務?割?31?確?務?確?務?尺?務?2.3.2?BioAutomata?BioAutomata?模?DBTL?割?1

19、%?77%?務?尺?iBioFAB?BioAutomata?撐練?割?DBTL?去?iBioFAB?BioAutomata?研?去?BioAutomata?研?BioAutomata?撐練?/?-?GC-MS?-?LC-MS?告?撐練?尺?iBioFAB?研?模?32?22.?務?BioAutomata?研?務?研?研?Nature?Communications?A.?BioAutomata?研?研?BioAutomata?iBioFAB?研?研?研?B.?研?尺?尺?封 33?尺?研?務?務?割?務?模?C.?尺?GP?尺?割?尺?告?96?D.?割?務?導?導?務務?務?撐練?割?務?-?

20、務?務?研?務?割?撐練?割?DNA?割?封?封?2.4?-?務?務?務?去?務?34?iBioFoundry?BT+IT?+?iBioFoundry?DNA?研割?務?匹?務?務?務?DNA?HEPA?割?iBioFoundry?1.?2.?3.?務?4.?務?5.?務?6.?研?模?7.?模?撐?8.?2.4.1?DNA?的?導?務?F7?模?PCR?F7?35?PCR?去?割?模?0.5ml?-80C?Arktic?SPT?labtech?F7?模?iBioFoundry?iBioFoundry?iBioFoundry?2.4.2?9?PCR 導?PCR?DNA?1.?去?模?PCR?2

21、.?PCR?3.?PCR?36?23.?Synthetic?Biology?Journal?24.?Synthetic?Biology?Journal?37?25.?Synthetic?Biology?Journal?2.4.3?務?研?撐?iBioFoundry?模?38?PCR?研 OD?研?OD?研?撐?研?研?務?務?研?務?研?1.?研?OD?研?2.?研?研?撐?3.?研?研?26.?Synthetic?Biology?Journal?2.4.4 iBioFoundry?1.?iBioFoundry 務?割?務?39?iBioFoundry?DNA?2.?iBioFoundry?務

22、?務?iBioFoundry?務?3.?務?iBioFoundry 務?務?40?3?展?-?-?-?封?封?告?務?割?20?割?封?務?割模?去?割?務?封?歷?撐練?割?2018?6?15?去?去?封?1.?2.模?撐?3.?的?務?4.?夠?封?封?3.1?去?匹?撐練?41?研割?,?封?務?去?研?研?3.2 SDLs?-?SDLs?覆?1.?TRY?Titer?Rate?Yield?務?TRY?去?確?-?-?告?務?2.?去?3.?4.?告?務?5.確?/?導?確?務?SDLs?割?SDL?撐練?SDLs?SDLs?SDLs?SDLs?研?務?SDLs?42?封?撐?匹?研?覆

23、?SDLs?27.?SDLs?SDLs?務?SDLs?務?SDLs?SDLs?夠?確?SDL1?SDL2?SDLs?務?研?封?撐練?ScienceDirect?43?3.3?SDLs?模?SDLs?覆?研?封?SDLs?務?告?SDLs?誘務?封?導?DNA?去?導?務?研?44?4?,?,?,?,?&?.?(2023).?.?,?39(2),?11.?,?,?,?,?,?&?.?(2021).?.?,?37(3),?37.?.?(2018).?:?.?,33(11),?1135-1149.?.?(2022).?:?.?,?38(11),?11.?,?,?,?,?,?&?.?(2021).?

24、.?,?2(6),?13.?,?.?(2023).?.?.?(2022).?.?,?,?,?,?.?(2022).?.?,?,?,?,?.?(2022).?.?2022?-?-?4Q?2021?Synthetic?Biology?Venture?Investment?Report?Synbiobeta?,?,?&?.?ibiofoundry?.?,?1-14.?Jinming,?C.?,?Bingzhao,?Z.?,?Yingfei,?M.?A.?,?Xiongfei,?F.?U.?,?Meng,?W.?,?&?Chenli,?L.?.?(2018).?Engineering?platform

25、s?for?synthetic?biology?research.?(11).?Yu,?T.,?Boob,?A.?G.,?Singh,?N.,?Su,?Y.,?&?Zhao,?H.?(2023).?In?vitro?continuous?protein?evolution?empowered?by?machine?learning?and?automation.?Cell?systems,?S2405-4712(23)00115-1.?Advance?online?publication.?Martin,?H.?G.,?Radivojevic,?T.,?Zucker,?J.,?Bouchard

26、,?K.,?Sustarich,?J.,?Peisert,?S.,?Arnold,?D.,?Hillson,?N.,?Babnigg,?G.,?Marti,?J.?M.,?Mungall,?C.?J.,?Beckham,?G.?T.,?Waldburger,?L.,?Carothers,?J.,?Sundaram,?S.,?Agarwal,?D.,?Simmons,?B.?A.,?Backman,?T.,?Banerjee,?D.,?Tanjore,?D.,?Singh,?A.?(2023).?Perspectives?for?self-driving?labs?in?synthetic?bi

27、ology.?Current?opinion?in?biotechnology,?79,?102881.?Gurdo,?N.,?Volke,?D.?C.,?McCloskey,?D.,?&?Nikel,?P.?I.?(2023).?Automating?the?design-build-test-learn?cycle?towards?next-generation?bacterial?cell?factories.?New?biotechnology,?74,?1?15.?Carbonell,?P.,?Radivojevic,?T.,?&?Garca?Martn,?H.?(2019).?Op

28、portunities?at?the?Intersection?of?Synthetic?Biology,?Machine?Learning,?and?Automation.?ACS?synthetic?biology,?8(7),?1474?1477.?HamediRad,?M.,?Chao,?R.,?Weisberg,?S.,?Lian,?J.,?Sinha,?S.,?&?Zhao,?H.?(2019).?Towards?a?fully?automated?algorithm?driven?platform?for?biosystems?design.?Nature?communicati

29、ons,?10(1),?5150.?Chao,?R.,?Liang,?J.,?Tasan,?I.,?Si,?T.,?Ju,?L.,?&?Zhao,?H.?(2017).?Fully?Automated?One-Step?Synthesis?of?Single-Transcript?TALEN?Pairs?Using?a?Biological?Foundry.?ACS?synthetic?biology,?6(4),?678?685.?Liu,?L.,?Huang,?Y.,?&?Wang,?H.?H.?(2023).?Fast?and?efficient?template-mediated?sy

30、nthesis?of?genetic?variants.?Nature?methods,?20(6),?841?848.?Enghiad,?B.,?Xue,?P.,?Singh,?N.,?Boob,?A.?G.,?Shi,?C.,?Petrov,?V.?A.,?Liu,?R.,?Peri,?S.?S.,?Lane,?S.?T.,?Gaither,?E.?D.,?&?Zhao,?H.?(2022).?PlasmidMaker?is?a?versatile,?automated,?and?high?throughput?end-to-end?platform?for?plasmid?construction.?Nature?communications,?13(1),?2697.?Smanski,?M.?J.,?Mead,?D.,?Gustafsson,?C.,?&?Thomas,?M.?G.?(2017).?Meeting?Report?for?Synthetic?Biology?for?Natural?Products?2017:?The?Interface?of?(Meta)Genomics,?Machine?Learning,?and?Natural?Product?Discovery.?ACS?synthetic?biology,?6(5),?737?743.?