REMEDIUMREMEDIUM1561-59362658-3534Joint-Stock Company Chicot95310.21518/1561-5936-2020-4-5-6-79-86Original ArticleAdvances in synthetic biology and regulatory policy of the stateMokhovA. A.noemail@neicon.ruChaplenkoA. A.noemail@neicon.ruYavorskiyA. N.noemail@neicon.ruKutafin Moscow State Law University (MSAL)National Research University Higher School of Economics (HSE)Pushchino State Institute of Natural Science041220204-6798618032022Copyright © 2020,2020Synthetic biology is a new interdisciplinary area of research applies the principles of engineering design in genetic and biomedical research. Progress in the development of tools used to modify natural biological systems (or used for creation of new ones) has allowed the development of traditional biomedicine and genomics. At the beginning of this review article, we look at the key achievements of synthetic biology over the past ten years. Despite the fact that the contribution of synthetic biology to fundamental research in the field of biology, medicine, ecology and other life sciences is undeniable, the potential risks for biological safety and security associated with the further development synthetic biology also require attention. This problem has become particularly relevant in recent years, as the technology becomes less expensive, more advanced and affordable. A brief assessment of the risks associated with the possible misuse or abuse of synthetic biology technologies is given from the point of view of danger to humanity and nature as a whole. To solve the problems arising due to the rapid progress of synthetic biology, technical, ethical and legal measures have been developed and planned.synthetic biologyachievementsrisksscientific ethicslegal regulationсинтетическая биологиядостижениярискинаучная этикаправовое регулирование[Gibson D.G., Benders G.A., Andrews-Pfannkoch C. et al. Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome. Science. 2008;319(5867):1215. doi: 10.1126/science.1151721.][Gibson D.G., Glass J.I., Lartigue C. et al. Creation of a bacterial cell controlled by a chemically synthesized genome. Science. 2010;329(5987):52-56. doi: 10.1126/science.1190719.][Dymond J.S., Richardson S.M., Coombes C.E. et al. Synthetic chromosome arms function in yeast and generate phenotypic diversity by design. Nature. 2011;477(7365):471-476.][Shao Y., Lu N., Wu Z., Cai C. et al. Creating a functional single- chromosome yeast. Nature. 2018;560(7718):331-335. doi: 10.1038/ s41586-018-0382-x.][Scientists Announce HGP-Write, Project to Synthesize the Human Genome - The New York Times. Available at: https://www. nytimes.com/2016/06/03/science/human-genome-project- write-synthetic-dna.html.][Hirao I., Kimoto M., Yamashige R. Natural versus artificial creation of base pairs in DNA: Origin of nucleobases from the perspectives of unnatural base pair studies. Acc Chem Res. 2012;45(12):2055-2065. doi: 10.1021/ar200257x.][Malyshev D.A., Dhami K., Lavergne T. et al. A semi-synthetic organism with an expanded genetic alphabet. Nature. 2014;509(7500):385-388. doi: 10.1038/nature13314.][Si T., Zhao H. A brief overview of synthetic biology research programs and roadmap studies in the United States. Synth Syst Biotechnol. 2016;1(4):258-264. doi: 10.1016/j.synbio.2016.08.003.][Ajikumar P.K., Xiao W.H., Tyo K.E. et al. Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science. 2010;330(6000):70-74. doi: 10.1126/science.1191652.][Seo S.W., Yang J.S., Kim I. et al. Predictive design of mRNA trans- lation initiation region to control prokaryotic translation efficiency. Metab Eng. 2013;15:67-74. doi: 10.1016/j.ymben.2012.10.006.][Angov E., Legler P.M., Mease R.M. Adjustment of codon usage frequencies by codon harmonization improves protein expression and folding. Methods Mol Biol. 2011;705:1-13. doi: 10.1007/978-1- 61737-967-3_1.][Ro D.K., Paradise E.M., Ouellet M. et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature. 2006;440(7086):940-943. doi: 10.1038/nature04640.][Coleman J.R., Papamichail D., Skiena S. et al. Virus attenu- ation by genome-scale changes in codon pair bias. Science. 2008;320(5884):1784-1787. doi: 10.1126/science.1155761.][Anderson J.C., Clarke E.J., Arkin A.P., Voigt C.A. et al. Environmentally controlled invasion of cancer cells by engi- neered bacteria. J Mol Biol. 2006;355(4):619-627. doi: 10.1016/j. jmb.2005.10.076.][Royo J.L., Becker P.D., Camacho E.M. et al. In vivo gene regula- tion in Salmonella spp. by a salicylate-dependent control circuit. Nat Methods. 2007;4(11):937-942. doi: 10.1038/nmeth1107.][Georgianna D.R., Mayfield S.P. Exploiting diversity and syn- thetic biology for the production of algal biofuels. Nature. 2012;488(7411):329-335. doi: 10.1038/nature11479.][O’Neill B.M., Mikkelson K.L., Gutierrez N.M. et al. An exogenous chloroplast genome for complex sequence manipulation in algae. Nucleic Acids Res. 2012;40(6):2782-2792. doi: 10.1093/nar/gkr1008.][Scognamiglio V., Antonacci A., Lambreva M.D., Litescu S.C., Rea G. Synthetic biology and biomimetic chemistry as converg- ing technologies fostering a new generation of smart biosen- sors. Biosens Bioelectron. 2015;74:1076-1086. doi: 10.1016/j. bios.2015.07.078.][Pardee K., Green A.A., Ferrante T. et al. Paper-based syn- thetic gene networks. Cell. 2014;159(4):940-954. doi: 10.1016/j. cell.2014.10.004.][Pardee K., Green A.A., Takahashi M.K. et al. Rapid, Low- Cost Detection of Zika Virus Using Programmable Biomolecular Components. Cell. 2016;165(5):1255-1266. doi: 10.1016/j. cell.2016.04.059.][Nordmann B.D. Issues in biosecurity and biosafety. Int J Antimicrob Agents. 2010;36(Suppl 1):66-69. doi: 10.1016/j.ijantimi- cag.2010.06.025.][Li L., Degardin M., Lavergne T. et al. Natural-like replication of an unnatural base pair for the expansion of the genetic alphabet and biotechnology applications. J Am Chem Soc. 2014;136(3):826-829. doi: 10.1021/ja408814g.][Acevedo-Rocha C.G., Budisa N. Xenomicrobiology: a roadmap for genetic code engineering. Microb Biotechnol. 2016;9(5):666-676. doi: 10.1111/1751-7915.12398.][Nielsen K.M., Johnsen P.J., Bensasson D., Daffonchio D. Release and persistence of extracellular DNA in the environment. Environ Biosafety Res. 2007;6(1-2):37-53. doi: 10.1051/ebr:2007031.][Hewett J.P., Wolfe A.K., Bergmann R.A., Stelling S.C. Human health and environmental risks posed by synthetic biology R&D for energy applications: A literature analysis. Appl Biosaf. 2016;21(4):177-184. doi: 10.1177/1535676016672377.][Gallagher R.R., Patel J.R., Interiano A.L., Rovner A.J., Isaacs F.J. Multilayered genetic safeguards limit growth of microorganisms to defined environments. Nucleic Acids Res. 2015;43(3):1945-1954. doi: 10.1093/nar/gku1378.][Medaglia M.L.G., Moussatché N., Nitsche A. et al. Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus. J Virol. 2015;89(23):11909-11925. doi: 10.1128/JVI.01833-15.][Lai H.E., Canavan C., Cameron L. et al. Synthetic Biology and the United Nations. Trends in Biotechnology. 2019;37(11):1146-1151. doi: 10.1016/j.tibtech.2019.05.011.][Zhang Q., Xing H.L., Wang Z.P. et al. Potential high-frequency off-target mutagenesis induced by CRISPR/Cas9 in Arabidopsis and its prevention. Plant Mol Biol. 2018;96(4-5):445-456. doi: 10.1007/ s11103-018-0709-x.][Kuhlau F., Eriksson S., Evers K., Höglund A.T. Taking due care: Moral obligations in dual use research. Bioethics. 2008;22(9):477, doi: 10.1111/j.1467-8519.2008.00695.x.][Top U.S. Intelligence Official Calls Gene Editing a WMD Threat - MIT Technology Review. Available at: https://www.technolo- gyreview.com/s/600774/top-us-intelligence-official-calls-gene- editing-a-wmd-threat/ (accessed: 06.02.2020).][Ehni H.J. Dual us1e and the ethical responsibility of scientists. Arch Immunol Ther Exp (Warsz). 2008;56(3):147-52. doi: 10.1007/ s00005-008-0020-7.][Buhk H.J. Synthetic biology and its regulation in the European Union. N Biotechnol. 2014;31(6):528-531. doi: 10.1016/j. nbt.2014.02.007.][Moon T.S., Lou C., Tamsir A., Stanton B.C., Voigt C.A. Genetic programs constructed from layered logic gates in single cells. Nature. 2012;491(7423):249-253. doi: 10.1038/nature11516.][Heider D., Pyka M., Barnekow A. DNA watermarks in non-coding regulatory sequences. BMC Res Notes. 2009;2:125. doi: 10.1186/1756- 0500-2-125.][Jupiter D.C., Ficht T.A., Samuel J., Qin Q.M., de Figueiredo P. DNA watermarking of infectious agents: Progress and prospects. PLoS Pathog. 2010;6(6):e1000950. doi: 10.1371/journal.ppat.1000950.][Proposal for the development of a model code of conduct for biological scientists under the Biological Weapons Convention. BWC / CONF.VIII / WP.30. Available at: https://www.unog. ch/80256EDD006B8954/(httpAssets)/9219B3032A7BAD73C12582E A00294C2B/$file/Yang+Xue.pdf. РЕМЕДИУМ | 2020;(4-5-6)]