A survey of enabling technologies in synthetic biology

Journal of Biological Engineering

Drew Endy¹  Linda J Kahl¹ 

[1] Bioengineering Department, Stanford University, Y2E2 Room 269C, 473 Via Ortega, Stanford, CA, 94305-4201, USA

关键词: Regulation;    Licensing;    Intellectual property rights;    Survey;    Enabling technologies;    Biological engineering;    Synthetic biology;   

Others  :  805648
DOI  :  10.1186/1754-1611-7-13

 received in 2012-12-19, accepted in 2013-04-30,  发布年份 2013

【 摘 要 】

Background

Realizing constructive applications of synthetic biology requires continued development of enabling technologies as well as policies and practices to ensure these technologies remain accessible for research. Broadly defined, enabling technologies for synthetic biology include any reagent or method that, alone or in combination with associated technologies, provides the means to generate any new research tool or application. Because applications of synthetic biology likely will embody multiple patented inventions, it will be important to create structures for managing intellectual property rights that best promote continued innovation. Monitoring the enabling technologies of synthetic biology will facilitate the systematic investigation of property rights coupled to these technologies and help shape policies and practices that impact the use, regulation, patenting, and licensing of these technologies.

Results

We conducted a survey among a self-identifying community of practitioners engaged in synthetic biology research to obtain their opinions and experiences with technologies that support the engineering of biological systems. Technologies widely used and considered enabling by survey participants included public and private registries of biological parts, standard methods for physical assembly of DNA constructs, genomic databases, software tools for search, alignment, analysis, and editing of DNA sequences, and commercial services for DNA synthesis and sequencing. Standards and methods supporting measurement, functional composition, and data exchange were less widely used though still considered enabling by a subset of survey participants.

Conclusions

The set of enabling technologies compiled from this survey provide insight into the many and varied technologies that support innovation in synthetic biology. Many of these technologies are widely accessible for use, either by virtue of being in the public domain or through legal tools such as non-exclusive licensing. Access to some patent protected technologies is less clear and use of these technologies may be subject to restrictions imposed by material transfer agreements or other contract terms. We expect the technologies considered enabling for synthetic biology to change as the field advances. By monitoring the enabling technologies of synthetic biology and addressing the policies and practices that impact their development and use, our hope is that the field will be better able to realize its full potential.

【 授权许可】

   
2013 Kahl and Endy; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, et al.: Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 2006, 440:940-943.
• [2]Ajikumar PK, Xiao WH, Tyo KE, Wang Y, Simeon F, et al.: Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 2010, 330:70-74.
• [3]Colin VL, Rodriguez A, Cristobal HA: The role of synthetic biology in the design of microbial cell factories for biofuel production. J Biomed Biotechnol 2011, 2011:601834.
• [4]Georgianna DR, Mayfield SP: Exploiting diversity and synthetic biology for the production of algal biofuels. Nature 2012, 488:329-335.
• [5]Bonnet J, Subsoontorn P, Endy D: Rewritable digital data storage in live cells via engineered control of recombination directionality. Proc Natl Acad Sci U S A 2012, 109:8884-8889.
• [6]Church GM, Gao Y, Kosuri S: Next-generation digital information storage in DNA. Science 2012, 337:1628.
• [7]Ortiz ME, Endy D: Engineered cell-cell communication via DNA messaging. J Biol Eng 2012, 6:16.
• [8]Bonnet J, Yin P, Ortiz ME, Subsoontorn P, Endy D: Amplifying genetic logic gates. Science 2013, 340:599-603.
• [9]Lutz R, Bujard H: Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements. Nucleic Acids Res 1997, 25:1203-1210.
• [10]Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, et al.: Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988, 239:487-491.
• [11]Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, et al.: Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985, 230:1350-1354.
• [12]Oldenburg KR, Vo KT, Michaelis S, Paddon C: Recombination-mediated PCR-directed plasmid construction in vivo in yeast. Nucleic Acids Res 1997, 25:451-452.
• [13]Etter PD, Preston JL, Bassham S, Cresko WA, Johnson EA: Local de novo assembly of RAD paired-end contigs using short sequencing reads. PLoS One 2011, 6:e18561.
• [14]Leguia M, Brophy J, Densmore D, Anderson JC: Automated assembly of standard biological parts. Methods Enzymol 2011, 498:363-397.
• [15]Ochman H, Gerber AS, Hartl DL: Genetic applications of an inverse polymerase chain reaction. Genetics 1988, 120:621-623.
• [16]Horton RM, Hunt HD, Ho SN, Pullen JK, Pease LR: Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension. Gene 1989, 77:61-68.
• [17]Lloyd D, Robinson K, Garside E, Fedor J, Ridgway D, et al.: BBF RFC 47: BioBytes Assembly Standard. 2009. http://dspace.mit.edu/handle/1721.1/49518 webcite
• [18]Isaacs FJ, Carr PA, Wang HH, Lajoie MJ, Sterling B, et al.: Precise manipulation of chromosomes in vivo enables genome-wide codon replacement. Science 2011, 333:348-353.
• [19]Morgan M, Grimshaw A: High-throughput computing in the sciences. Methods Enzymol 2009, 467:197-227.
• [20]Rothberg JM, Hinz W, Rearick TM, Schultz J, Mileski W, et al.: An integrated semiconductor device enabling non-optical genome sequencing. Nature 2011, 475:348-352.
• [21]Pan S, Aebersold R, Chen R, Rush J, Goodlett DR, et al.: Mass spectrometry based targeted protein quantification: methods and applications. J Proteome Res 2009, 8:787-797.
• [22]Ranganathan S, Suthers PF, Maranas CD: OptForce: an optimization procedure for identifying all genetic manipulations leading to targeted overproductions. PLoS Comput Biol 2010, 6:e1000744.
• [23]Walls D, McGrath R, Loughran ST: A digest of protein purification. Methods Mol Biol 2011, 681:3-23.
• [24]Sharan SK, Thomason LC, Kuznetsov SG, Court DL: Recombineering: a homologous recombination-based method of genetic engineering. Nat Protoc 2009, 4:206-223.
• [25]Larson DR: What do expression dynamics tell us about the mechanism of transcription? Curr Opin Genet Dev 2011, 21:591-599.
• [26]Arkin A: Setting the standard in synthetic biology. Nat Biotechnol 2008, 26:771-774.
• [27]Endy D: Foundations for engineering biology. Nature 2005, 438:449-453.
• [28]Guo L, Liang T, Lu Z: A comprehensive study of multiple mapping and feature selection for correction strategy in the analysis of small RNAs from SOLiD sequencing. Biosystems 2011, 104:87-93.
• [29]Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, et al.: Breaking the code of DNA binding specificity of TAL-type III effectors. Science 2009, 326:1509-1512.
• [30]Gibson DG, Benders GA, Andrews-Pfannkoch C, Denisova EA, Baden-Tillson H, et al.: Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome. Science 2008, 319:1215-1220.
• [31]Jaschke PR, Lieberman EK, Rodriguez J, Sierra A, Endy D: A fully decompressed synthetic bacteriophage oX174 genome assembled and archived in yeast. Virology 2012, 434:278-284.
• [32]Rai A, Boyle J: Synthetic biology: caught between property rights, the public domain, and the commons. PLoS Biol 2007, 5:e58.
• [33]Calvert J: Ownership and sharing in synthetic biology: a ‘diverse ecology’ of the open and the proprietary. BioSocieties 2012, 7:169-187.
• [34]Oye KA, Wellhausen R: The intellectual commons and property in synthetic biology. In Synthetic Biology: The Technoscience and Its Societal Consequences. Edited by Schmidt M, Kelle A, Ganguli-Mitra A, de Vriend H. Heidelberg, Germany: Springer; 2009:121-140.
• [35]Rutz B: Synthetic biology and patents. A European perspective. EMBO Rep 2009, 10(Suppl 1):S14-S17.
• [36]Henkel J, Maurer SM: Parts, property and sharing. Nat Biotechnol 2009, 27:1095-1098.
• [37]Bertani G: Studies on lysogenesis. I. The mode of phage liberation by lysogenic Escherichia coli. J Bacteriol 1951, 62:293-300.
• [38]Hollander DH, Nell EE: Improved preservation of Treponema pallidum and other bacteria by freezing with glycerol. Appl Microbiol 1954, 2:164-170.
• [39]Howard DH: The preservation of bacteria by freezing in glycerol broth. J Bacteriol 1956, 71:625.
• [40]Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA 3rd, et al.: Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 2009, 6:343-345.
• [41]Synthetic Genomics, Inc. Press Release: February 7, 2012. Synthetic Genomics, Inc. Announces Agreement with New England Biolabs to Launch Gibson Assembly™ Master Mix Product for Synthetic and Molecular Biology Applications. Available: http://www.syntheticgenomics.com/media/press/020712.html webcite. Accessed 11.20.2012
• [42]New England BioLabs, Inc., Gibson Assembly™ Master Mix, Limited Use Label License. Available: http://www.neb.com/nebecomm/products_intl/productE2611.asp webcite. Accessed 11.20.2012
• [43]ATCC Press Release: June 18, 2012. ATCC Announces Agreement with Life Technologies Corporation to Sell and Distribute Green Fluorescent Protein (GFP)-based Materials. Available: http://www.prweb.com/releases/2012/6/prweb9612892.htm webcite Accessed 11.29.2012
• [44]Mutalik VK: Expression Operating Unit: Origins and Current Status. 2010. [BIOFAB Community Meeting] June 19, 2010. http://www.biofab.org/sites/default/files/BIOFAB_CommunityMeeting1_Vivek.pdf webcite.
• [45]Mutalik VK, Guimaraes JC, Cambray G, Lam C, Christoffersen MJ, et al.: Precise and reliable gene expression via standard transcription and translation initiation elements. Nat Methods 2013, 10:354-360.
• [46]Mutalik VK, Guimaraes JC, Cambray G, Mai QA, Christoffersen MJ, et al.: Quantitative estimation of activity and quality for collections of functional genetic elements. Nat Methods 2013, 10:347-353.
• [47]Kelly JR, Rubin AJ, Davis JH, Ajo-Franklin CM, Cumbers J, et al.: Measuring the activity of BioBrick promoters using an in vivo reference standard. J Biol Eng 2009, 3:4.
• [48]Rai A: Unstandard standarization: the case of biology. Communications of the ACM 2010, 53:37-39.
• [49]Torrance AW, Kahl LJ: Bringing standards to life: synthetic biology standards and intellectual property. Santa Clara Computer & High Tech L J. 2013. in press
• [50]Kumar S, Rai A: Synthetic biology: the intellectual property puzzle. Texas Law Review 2007, 85:1745-1768.
• [51]Bekkers R, West J: The limits to IPR standardization policies as evidenced by strategic patenting in UTMS. Telecommunications Policy 2009, 33:80-97.
• [52]Bekkers R, Iverson E, Blind K: Emerging ways to address the reemerging conflict between patenting and technological standardization. Indus Corp Change 2012, 21:901-931.
• [53]U.S. Dep’t of Justice, Fed Trade Comm'n: Antitrust Enforcement and Intellectual Property Rights: Promoting Innovation and Competition. 2007. http://www.usdoj.gov/atr/public/hearings/ip/222655.pdf webcite
• [54]U.S. Dep’t of Justice, U.S. Patent and Trademark Office: Policy Statement on Remedies for Standards-Essential Patents Subject to Voluntary F/Rand Commitments. 2013. http://www.justice.gov/atr/public/guidelines/290994.pdf webcite
• [55]Oldham P, Hall S, Burton G: Synthetic biology: mapping the scientific landscape. PLoS One 2012, 7:e34368.
• [56]Carlson R: The changing economics of DNA synthesis. Nat Biotechnol 2009, 27:1091-1094.
• [57]U.S. Department of Health and Human Services, National Institutes of Health: NIH Guidelines for Research Involving Recombinant DNA Molecules, revised October 2011. available at http://oba.od.nih.gov/rdna/nih_guidelines_oba.html webcite
• [58]U.S. Department of Health and Human Services, National Institutes of Health: Screening Framework Guidance for Synthetic Double-Stranded DNA Providers, October 2010. available at http://www.phe.gov/Preparedness/legal/guidance/syndna/Documents/syndna-guidance.pdf webcite
• [59]Smolke CD: Building outside of the box: iGEM and the BioBricks foundation. Nat Biotechnol 2009, 27:1099-1102.
• [60]Carlson JM, Heckerman D, Shani G: Estimating false discovery rates for contingency tables. Microsoft Research Tech Report MSR-TR-2009-53. 2009. available at http://research.microsoft.com/apps/pubs/?id=80571 webcite
• [61]Knight T: Idempotent Vector Design for Standard Assembly of Biobricks. MIT Synthetic Biology Working Group Technical Report. 2003. http://dspace.mit.edu/handle/1721.1/21168 webcite
• [62]Anderson JC, Dueber JE, Leguia M, Wu GC, Goler JA, et al.: BglBricks: A flexible standard for biological part assembly. J Biol Eng 2010, 4:1.
• [63]Phillips IE, Silver PA: BBF RFC 23: A New BioBrick Assembly Strategy Designed for Facile Protein Engineering. 2006. http://dspace.mit.edu/handle/1721.1/32535 webcite
• [64]Muller KM, Arndt KM, Grunberg R, iGEM 2007 Team Freiburg: BBF RFC 25: Fusion Protein (Freiburg) BioBrick assembly standard. 2009. http://dspace.mit.edu/handle/1721.1/45140 webcite
• [65]Peisajovich SG, Horwitz A, Hoeller O, Rhau B, Lim WA: BBF RFC 28: A method for combinatorial multi-part assembly based on the Type IIs restriction enzyme AarI. 2009. http://dspace.mit.edu/handle/1721.1/46721 webcite
• [66]Quan J, Tian J: Circular polymerase extension cloning of complex gene libraries and pathways. PLoS One 2009, 4:e6441.
• [67]Shao Z, Zhao H, Zhao H: DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways. Nucleic Acids Res 2009, 37:e16.
• [68]Hartley JL, Temple GF, Brasch MA: DNA cloning using in vitro site-specific recombination. Genome Res 2000, 10:1788-1795.
• [69]Sarrion-Perdigones A, Falconi EE, Zandalinas SI, Juarez P, Fernandez-del-Carmen A, et al.: GoldenBraid: an iterative cloning system for standardized assembly of reusable genetic modules. PLoS One 2011, 6:e21622.
• [70]Engler C, Kandzia R, Marillonnet S: A one pot, one step, precision cloning method with high throughput capability. PLoS One 2008, 3:e3647.
• [71]Weber E, Engler C, Gruetzner R, Werner S, Marillonnet S: A modular cloning system for standardized assembly of multigene constructs. PLoS One 2011, 6:e16765.
• [72]Zhang Y, Werling U, Edelmann W: SLiCE: a novel bacterial cell extract-based DNA cloning method. Nucleic Acids Res 2012, 40:e55.
• [73]Li MZ, Elledge SJ: Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC. Nat Methods 2007, 4:251-256.
• [74]Carr PA, Church GM: Genome engineering. Nat Biotechnol 2009, 27:1151-1162.
• [75]Klock HE, Lesley SA: The polymerase incomplete primer extension (PIPE) method applied to high-throughput cloning and site-directed mutagenesis. Methods Mol Biol 2009, 498:91-103.
• [76]Bitinaite J, Rubino M, Varma KH, Schildkraut I, Vaisvila R, et al.: USER friendly DNA engineering and cloning method by uracil excision. Nucleic Acids Res 2007, 35:1992-2002.
• [77]Endy D, Deese I, MIT Synthetic Biology Working Group, and illustrated by Wadey C: Adventures in Synthetic Biology. A comic book. 2005. available online at http://dspace-test.mit.edu/handle/1721.1/46337 webcite
• [78]Velten L, Iwamoto N, Hiller C, Uckelmann H, Zhu C, et al.: BBF RFC 41: Units for Promoter Measurement in Mammalian Cells. 2009. http://dspace.mit.edu/handle/1721.1/49501 webcite
• [79]Galdzicki M, Wilson ML, Rodriguez CA, Pocock MR, Oberortner E, et al.: BBF RFC 87: Synthetic Biology Open Language (SBOL) Version 1.1.0. 2012. http://dspace.mit.edu/handle/1721.1/73909 webcite
• [80]Johnson J, Galdzicki M, Sauro HM: BBF RFC 68: Standard for the Electronic Distribution of SBOLv Diagrams. 2010. http://dspace.mit.edu/handle/1721.1/60086 webcite
• [81]Quinn JP, Beal J, Bhatia S, Cai P, Chen J, et al.: BBF RFC 93: Synthetic Biology Open Language Visual (SBOL Visual), version 1.0.0 . 2013. http://dspace.mit.edu/handle/1721.1/78249 webcite
• [82]Canton B, Labno A, Endy D: Refinement and standardization of synthetic biological parts and devices. Nat Biotechnol 2008, 26:787-793.
• [83]Lee TS, Krupa RA, Zhang F, Hajimorad M, Holtz WJ, et al.: BglBrick vectors and datasheets: a synthetic biology platform for gene expression. J Biol Eng 2011, 5:12.
• [84]Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, et al.: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25:3389-3402.
• [85]Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, et al.: Clustal W and clustal X version 2.0. Bioinformatics 2007, 23:2947-2948.
• [86]Kibbe WA: OligoCalc: an online oligonucleotide properties calculator. Nucleic Acids Res 2007, 35:W43-W46.
• [87]Stranneheim H, Lundeberg J: Stepping stones in DNA sequencing. Biotechnol J 2012, 7:1063-1073.
• [88]Bertani G: Lysogeny at mid-twentieth century: P1, P2, and other experimental systems. J Bacteriol 2004, 186:595-600.
• [89]Kocagoz T, Altin S, Turkyilmaz O, Tas I, Karaduman P, et al.: Efficiency of the TK culture system in the diagnosis of tuberculosis. Diagn Microbiol Infect Dis 2012, 72:350-357.
• [90]Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC: Green fluorescent protein as a marker for gene expression. Science 1994, 263:802-805.
• [91]Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, et al.: Programming cells by multiplex genome engineering and accelerated evolution. Nature 2009, 460:894-898.
• [92]Slusarczyk AL, Lin A, Weiss R: Foundations for the design and implementation of synthetic genetic circuits. Nat Rev Genet 2012, 13:406-420.