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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">regmedjournal</journal-id><journal-title-group><journal-title xml:lang="ru">Регенерация органов и тканей</journal-title><trans-title-group xml:lang="en"><trans-title>Регенерация органов и тканей</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2949-5938</issn><publisher><publisher-name>Общество регенеративной медицины</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.60043/2949-5938-2025-1-10-21</article-id><article-id custom-type="elpub" pub-id-type="custom">regmedjournal-104</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРЫ И КОММЕНТАРИИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEWS AND COMMENTS</subject></subj-group></article-categories><title-group><article-title>Эволюция подходов к манипуляции генетическим материалом живых объектов: от селекции к редактированию генома</article-title><trans-title-group xml:lang="en"><trans-title>Evolution of approaches to manipulating the genetic material of living objects: from selection to genome editing</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Стамбольский</surname><given-names>Д. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Stambolsky</surname><given-names>D. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Стамбольский Дмитрий Викторович — к.б.н., ведущий научный сотрудник, отдел научных программ и инновационных технологий, Университетская клиника, Медицинский научно-образовательный институт.</p><p>119192, Москва, Ломоносовский пр-т, д. 27, к. 10</p></bio><bio xml:lang="en"><p>Dmitry V. Stambolsky — Cand. Sci. (Biology), Leading Researcher, Department of Scientific Programs and Innovative Technologies, University Clinic, Medical Research and Educational Institute, Lomonosov Moscow State University.</p><p>119192, Moscow, Lomonosovsky Ave., 27/10</p></bio><email xlink:type="simple">stambolskydv@my.msu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Захарова</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Zakharova</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Захарова Алина Вячеславовна — аспирант, факультет фундаментальной медицины, Медицинский научно-образовательный институт.</p><p>119192, Москва, Ломоносовский пр-т, д. 27, к. 10</p></bio><bio xml:lang="en"><p>Alina V. Zakharova — PhD student, Faculty of Medicine, Medical Research and Educational Institute, Lomonosov Moscow State University.</p><p>119192, Moscow, Lomonosovsky Ave., 27/10</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Карагяур</surname><given-names>М. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Karagyaur</surname><given-names>M. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Карагяур Максим Николаевич — д.б.н., доцент кафедры биохимии и регенеративной биомедицины, старший научный сотрудник Центра регенеративной медицины, Медицинский научно-образовательный институт.</p><p>119192, Москва, Ломоносовский пр-т, д. 27, к. 10</p></bio><bio xml:lang="en"><p>Maxim N. Karagyaur — Dr. Sci. (Biology), Associate Professor, Department of Biochemistry and Regenerative Biomedicine, Senior Researcher, Center for Regenerative Medicine, Medical Research and Educational Institute, Lomonosov Moscow State University.</p><p>119192, Moscow, Lomonosovsky Ave., 27/10</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»<country>Россия</country></aff><aff xml:lang="en">Medical Research and Educational Institute, Lomonosov Moscow State University<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>05</day><month>04</month><year>2026</year></pub-date><volume>3</volume><issue>1</issue><fpage>10</fpage><lpage>21</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Стамбольский Д.В., Захарова А.В., Карагяур М.Н., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Стамбольский Д.В., Захарова А.В., Карагяур М.Н.</copyright-holder><copyright-holder xml:lang="en">Stambolsky D.V., Zakharova A.V., Karagyaur M.N.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.regmed-journal.ru/jour/article/view/104">https://www.regmed-journal.ru/jour/article/view/104</self-uri><abstract><p>Системы редактирования генома представляют собой мощный инструмент, способный прицельно модифицировать генетический материал в его природном контексте внутри живого организма. Благодаря таким удивительным возможностям системы редактирования нашли широкий спектр применения во всех сферах биологической науки и медицины. В данной рукописи мы проводим краткий исторический экскурс по вопросу возникновения и развития различных систем геномного редактирования. Эволюция данного направления сопровождалась грандиозными открытиями и вручением целого ряда Нобелевских премий. Отслеживая логику научной мысли в стремлении понять и модифицировать материальную основу наследственности, данная рукопись ставит своей целью сформировать у начинающих исследователей целостную картину об огромной вселенной (без преувеличения) систем геномного редактирования. Понимание же полноты всего спектра потенциальной активности систем редактирования обязывает исследователей к вдумчивому и ответственному их применению.</p></abstract><trans-abstract xml:lang="en"><p>Genome editing systems are powerful tools capable of precisely modifying genetic material in its natural context within a living organism. Due to these remarkable capabilities, editing systems have found a wide range of applications in all areas of biological science and medicine. In this review, we provide a brief historical overview of the origins and development of various genome editing systems. The evolution of this field has been accompanied by significant discoveries and the awarding of numerous Nobel Prizes. Tracing the logic of scientific thought in the quest to understand and modify the material basis of heredity, this manuscript aims to provide budding researchers with a comprehensive picture of the vast universe of genome editing systems. Understanding the full spectrum of potential activity of editing systems obliges researchers to use them thoughtfully and responsibly.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>системы редактирования генома</kwd><kwd>CRISPR/Cas9</kwd><kwd>TIGR/Tas</kwd><kwd>преимущества и ограничения систем геномного редактирования</kwd></kwd-group><kwd-group xml:lang="en"><kwd>genome editing systems</kwd><kwd>CRISPR/Cas9</kwd><kwd>TIGR/Tas</kwd><kwd>advantages and limitations of genome editing systems</kwd></kwd-group><funding-group xml:lang="ru"><funding-statement>Работа выполнена в рамках государственного задания ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова».</funding-statement></funding-group><funding-group xml:lang="en"><funding-statement>The study was carried out as part of Lomonosov Moscow State University state assignment.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Dahm R. Discovering DNA: Friedrich Miescher and the early years of nucleic acid research. Hum Genet. 2008;122(6):565–581. DOI: 10.1007/s00439-007-0433-0</mixed-citation><mixed-citation xml:lang="en">Dahm R. Discovering DNA: Friedrich Miescher and the early years of nucleic acid research. Hum Genet. 2008;122(6):565–581. DOI: 10.1007/s00439-007-0433-0</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Watson JD, Crick FHC. Molecular structure of nucleic acids. Nature. 1953;171(4356):737–738. DOI: 10.1038/171737a0</mixed-citation><mixed-citation xml:lang="en">Watson JD, Crick FHC. Molecular structure of nucleic acids. Nature. 1953;171(4356):737–738. DOI: 10.1038/171737a0</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Lehnert H, Berner T, Lang D, Beier S, Stein N, Himmelbach A, Kilian B, Keilwagen J. Insights into breeding history, hotspot regions of selection, and untapped allelic diversity for bread wheat breeding. Plant J. 2022;112(4):897–918. DOI: 10.1111/tpj.15952</mixed-citation><mixed-citation xml:lang="en">Lehnert H, Berner T, Lang D, Beier S, Stein N, Himmelbach A, Kilian B, Keilwagen J. Insights into breeding history, hotspot regions of selection, and untapped allelic diversity for bread wheat breeding. Plant J. 2022;112(4):897–918. DOI: 10.1111/tpj.15952</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Muller HJ. Artificial transmutation of the gene. Science. 1927;66(1699):84–87. DOI: 10.1126/science.66.1699.84</mixed-citation><mixed-citation xml:lang="en">Muller HJ. Artificial transmutation of the gene. Science. 1927;66(1699):84–87. DOI: 10.1126/science.66.1699.84</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Riaz M, Yasmeen E, Saleem B, Hameed MK, Saeed Almheiri MT, Saeed Al Mir RO, et al. Evolution of agricultural biotechnology is the paradigm shift in crop resilience and development: a review. Front Plant Sci. 2025;16:1585826. DOI: 10.3389/fpls.2025.1585826</mixed-citation><mixed-citation xml:lang="en">Riaz M, Yasmeen E, Saleem B, Hameed MK, Saeed Almheiri MT, Saeed Al Mir RO, et al. Evolution of agricultural biotechnology is the paradigm shift in crop resilience and development: a review. Front Plant Sci. 2025;16:1585826. DOI: 10.3389/fpls.2025.1585826</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Miescher F. Ueber die chemische Zusammensetzung der Eiterzellen. Hoppe-Seyler’s Med Chem. 1871;4:441–460.</mixed-citation><mixed-citation xml:lang="en">Miescher F. Ueber die chemische Zusammensetzung der Eiterzellen. Hoppe-Seyler’s Med Chem. 1871;4:441–460.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Altmann R. Die Elementarorganismen und ihre Beziehungen zu den Zellen. Leipzig: Veit &amp; Co., 1890.</mixed-citation><mixed-citation xml:lang="en">Altmann R. Die Elementarorganismen und ihre Beziehungen zu den Zellen. Leipzig: Veit &amp; Co., 1890.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Griffith F. The significance of pneumococcal types. J Hyg (Lond). 1928;27(2):113–159. DOI: 10.1017/S0022172400031879</mixed-citation><mixed-citation xml:lang="en">Griffith F. The significance of pneumococcal types. J Hyg (Lond). 1928;27(2):113–159. DOI: 10.1017/S0022172400031879</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Avery OT, MacLeod CM, McCarty M. Studies on the chemical nature of the substance inducing transformation. J Exp Med. 1944;79(2):137–158. DOI: 10.1084/jem.79.2.137</mixed-citation><mixed-citation xml:lang="en">Avery OT, MacLeod CM, McCarty M. Studies on the chemical nature of the substance inducing transformation. J Exp Med. 1944;79(2):137–158. DOI: 10.1084/jem.79.2.137</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Todd AR. Nucleotides, nucleosides, and nucleic acids. Angew Chem. 1958;70(1):1–17. DOI: 10.1002/anie.195800011</mixed-citation><mixed-citation xml:lang="en">Todd AR. Nucleotides, nucleosides, and nucleic acids. Angew Chem. 1958;70(1):1–17. DOI: 10.1002/anie.195800011</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Chargaff E. Chemical specificity of nucleic acids and mechanism of their enzymatic degradation. Experientia. 1950;6(6):201–209. DOI: 10.1007/BF02173653</mixed-citation><mixed-citation xml:lang="en">Chargaff E. Chemical specificity of nucleic acids and mechanism of their enzymatic degradation. Experientia. 1950;6(6):201–209. DOI: 10.1007/BF02173653</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Franklin RE, Gosling RG. Molecular configuration in sodium thymonucleate. Nature. 1953; 171:740–741. DOI: 10.1038/171740a0</mixed-citation><mixed-citation xml:lang="en">Franklin RE, Gosling RG. Molecular configuration in sodium thymonucleate. Nature. 1953; 171:740–741. DOI: 10.1038/171740a0</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Hershey AD, Chase M. Independent functions of viral protein and nucleic acid in the growth of bacteriophage. J Gen Physiol. 1952;36(1):39–56. DOI: 10.1085/jgp.36.1.39</mixed-citation><mixed-citation xml:lang="en">Hershey AD, Chase M. Independent functions of viral protein and nucleic acid in the growth of bacteriophage. J Gen Physiol. 1952;36(1):39–56. DOI: 10.1085/jgp.36.1.39</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Fraenkel-Conrat H, Singer B. Reconstitution of infectivity with ribonucleic acid and virus protein. Proc Natl Acad Sci USA. 1957;43(9):707–713. DOI: 10.1073/pnas.43.9.707</mixed-citation><mixed-citation xml:lang="en">Fraenkel-Conrat H, Singer B. Reconstitution of infectivity with ribonucleic acid and virus protein. Proc Natl Acad Sci USA. 1957;43(9):707–713. DOI: 10.1073/pnas.43.9.707</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Watson JD, Crick FHC. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature. 1953;171(4356):737–738. DOI: 10.1038/171737a0</mixed-citation><mixed-citation xml:lang="en">Watson JD, Crick FHC. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature. 1953;171(4356):737–738. DOI: 10.1038/171737a0</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Gamow G. Possible relation between deoxyribonucleic acid and protein structures. Nature. 1954;173:318. DOI: 10.1038/173318a0</mixed-citation><mixed-citation xml:lang="en">Gamow G. Possible relation between deoxyribonucleic acid and protein structures. Nature. 1954;173:318. DOI: 10.1038/173318a0</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Nirenberg MW, Matthaei JH. The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides. Proc Natl Acad Sci USA. 1961;47(10):1588–1602. DOI: 10.1073/pnas.47.10.1588</mixed-citation><mixed-citation xml:lang="en">Nirenberg MW, Matthaei JH. The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides. Proc Natl Acad Sci USA. 1961;47(10):1588–1602. DOI: 10.1073/pnas.47.10.1588</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Karagyaur MN, Rubtsov YP, Vasiliev PA, Tkachuk VA. Practical recommendations for improving efficiency and accuracy of the CRISPR/Cas9 genome-editing system. Biochemistry (Moscow). 2018;83(6):629–642. DOI: 10.1134/S0006297918060020</mixed-citation><mixed-citation xml:lang="en">Karagyaur MN, Rubtsov YP, Vasiliev PA, Tkachuk VA. Practical recommendations for improving efficiency and accuracy of the CRISPR/Cas9 genome-editing system. Biochemistry (Moscow). 2018;83(6):629–642. DOI: 10.1134/S0006297918060020</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975;94(3):441–448. DOI: 10.1016/0022-2836(75)90213-2</mixed-citation><mixed-citation xml:lang="en">Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975;94(3):441–448. DOI: 10.1016/0022-2836(75)90213-2</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Roberts RJ. Restriction enzymes and their use in molecular cloning. Annu Rev Biochem. 1976;45:485–528. DOI: 10.1146/annurev.bi.45.070176.002501</mixed-citation><mixed-citation xml:lang="en">Roberts RJ. Restriction enzymes and their use in molecular cloning. Annu Rev Biochem. 1976;45:485–528. DOI: 10.1146/annurev.bi.45.070176.002501</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Jackson DA, Symons RH and Berg P. Biochemical Method for Inserting New Genetic Information into DNA of Simian Virus 40: Circular SV40 DNA Molecules Containing Lambda Phage Genes and the Galactose Operon of Escherichia coli Proceedings of the National Academy of Sciences, Vol. 69, No. 10, 1972, pp. 2904-2909. DOI:10.1073/pnas.69.10.2904</mixed-citation><mixed-citation xml:lang="en">Jackson DA, Symons RH and Berg P. Biochemical Method for Inserting New Genetic Information into DNA of Simian Virus 40: Circular SV40 DNA Molecules Containing Lambda Phage Genes and the Galactose Operon of Escherichia coli Proceedings of the National Academy of Sciences, Vol. 69, No. 10, 1972, pp. 2904-2909. DOI:10.1073/pnas.69.10.2904</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Mullis K, Faloona F. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. DOI: 10.1016/0076-6879(87)55023-6</mixed-citation><mixed-citation xml:lang="en">Mullis K, Faloona F. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. DOI: 10.1016/0076-6879(87)55023-6</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Clerici M, et al. T lymphocyte-directed gene therapy for ADA-SCID: Initial trial results after 4 years. Science. 1995;270(5235):475–480. DOI: 10.1126/science.270.5235.475</mixed-citation><mixed-citation xml:lang="en">Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Clerici M, et al. T lymphocyte-directed gene therapy for ADA-SCID: Initial trial results after 4 years. Science. 1995;270(5235):475–480. DOI: 10.1126/science.270.5235.475</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab. 2003;80(1–2):148–158. DOI: 10.1016/j.ymgme.2003.08.016</mixed-citation><mixed-citation xml:lang="en">Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab. 2003;80(1–2):148–158. DOI: 10.1016/j.ymgme.2003.08.016</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Capecchi MR. Altering the genome by homologous recombination. Science. 1989;244(4910): 1288–1292. DOI: 10.1126/science.2660260</mixed-citation><mixed-citation xml:lang="en">Capecchi MR. Altering the genome by homologous recombination. Science. 1989;244(4910): 1288–1292. DOI: 10.1126/science.2660260</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Thomas KR, Capecchi MR. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell. 1987;51(3):503–512. DOI: 10.1016/0092-8674(87)90646-5</mixed-citation><mixed-citation xml:lang="en">Thomas KR, Capecchi MR. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell. 1987;51(3):503–512. DOI: 10.1016/0092-8674(87)90646-5</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Smithies O. The integration of homologous DNA sequences in mammalian chromosomes. Nature. 1985;317(6039):230–234. DOI: 10.1038/317230a0</mixed-citation><mixed-citation xml:lang="en">Smithies O. The integration of homologous DNA sequences in mammalian chromosomes. Nature. 1985;317(6039):230–234. DOI: 10.1038/317230a0</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Trudeau DL, Smith MA, Arnold FH. Innovation by homologous recombination. Curr Opin Chem Biol. 2013;17(6):902–909. DOI: 10.1016/j.cbpa.2013.10.007</mixed-citation><mixed-citation xml:lang="en">Trudeau DL, Smith MA, Arnold FH. Innovation by homologous recombination. Curr Opin Chem Biol. 2013;17(6):902–909. DOI: 10.1016/j.cbpa.2013.10.007</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Doetschman T, Gregg RG, Maeda N, Hooper ML, Melton DW, Thompson S, et al. Targetted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature. 1987;330(6148):576–578. DOI: 10.1038/330576a0</mixed-citation><mixed-citation xml:lang="en">Doetschman T, Gregg RG, Maeda N, Hooper ML, Melton DW, Thompson S, et al. Targetted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature. 1987;330(6148):576–578. DOI: 10.1038/330576a0</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Porteus MH, Baltimore D. Chimeric nucleases stimulate gene targeting in human cells. Science. 2003;300(5620):763. DOI: 10.1126/science.1078395</mixed-citation><mixed-citation xml:lang="en">Porteus MH, Baltimore D. Chimeric nucleases stimulate gene targeting in human cells. Science. 2003;300(5620):763. DOI: 10.1126/science.1078395</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Rouet P, Smih F, Jasin M. Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol Cell Biol. 1994;14(12):8096–8106. DOI: 10.1128/MCB.14.12.8096-8106.1994</mixed-citation><mixed-citation xml:lang="en">Rouet P, Smih F, Jasin M. Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol Cell Biol. 1994;14(12):8096–8106. DOI: 10.1128/MCB.14.12.8096-8106.1994</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Choulika A, Perrin A, Dujon B, Nicolas JF. Induction of homologous recombination in mammalian chromosomes by using the I-SceI system of Saccharomyces cerevisiae. Mol Cell Biol. 1995;15(4):1968–1973. DOI: 10.1128/MCB.15.4.1968-1973.1995</mixed-citation><mixed-citation xml:lang="en">Choulika A, Perrin A, Dujon B, Nicolas JF. Induction of homologous recombination in mammalian chromosomes by using the I-SceI system of Saccharomyces cerevisiae. Mol Cell Biol. 1995;15(4):1968–1973. DOI: 10.1128/MCB.15.4.1968-1973.1995</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Carroll D. Genome engineering with zinc-finger nucleases. Genetics. 2011;188(4):773–782. DOI: 10.1534/genetics.111.131433</mixed-citation><mixed-citation xml:lang="en">Carroll D. Genome engineering with zinc-finger nucleases. Genetics. 2011;188(4):773–782. DOI: 10.1534/genetics.111.131433</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Roberts RJ. Restriction endonucleases. CRC Crit Rev Biochem. 1976;4:123–164. DOI: 10.3109/10409237609105456</mixed-citation><mixed-citation xml:lang="en">Roberts RJ. Restriction endonucleases. CRC Crit Rev Biochem. 1976;4:123–164. DOI: 10.3109/10409237609105456</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Silva G, Poirot L, Galetto R, Smith J, Montoya G, Duchateau P, et al. Meganucleases and other tools for targeted genome engineering: perspectives and challenges. Curr Gene Ther. 2011;11(1):11–27. DOI: 10.2174/156652311794520111</mixed-citation><mixed-citation xml:lang="en">Silva G, Poirot L, Galetto R, Smith J, Montoya G, Duchateau P, et al. Meganucleases and other tools for targeted genome engineering: perspectives and challenges. Curr Gene Ther. 2011;11(1):11–27. DOI: 10.2174/156652311794520111</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Stoddard BL. Homing endonuclease structure and function. Q Rev Biophys. 2005;38(1):49–95. DOI: 10.1017/S0033583505004063</mixed-citation><mixed-citation xml:lang="en">Stoddard BL. Homing endonuclease structure and function. Q Rev Biophys. 2005;38(1):49–95. DOI: 10.1017/S0033583505004063</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Smith J, Grizot S, Arnould S, Duclert A, Epinat JC, Chames P, et al. A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences. Nucleic Acids Res. 2006;34(22):e149. DOI: 10.1093/nar/gkl720</mixed-citation><mixed-citation xml:lang="en">Smith J, Grizot S, Arnould S, Duclert A, Epinat JC, Chames P, et al. A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences. Nucleic Acids Res. 2006;34(22):e149. DOI: 10.1093/nar/gkl720</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Kim YG, Cha J, Chandrasegaran S. Hybrid restriction enzymes: zinc finger fusions to FokI cleavage domain. Proc Natl Acad Sci USA. 1996;93(3):1156–1160. DOI: 10.1073/pnas.93.3.1156</mixed-citation><mixed-citation xml:lang="en">Kim YG, Cha J, Chandrasegaran S. Hybrid restriction enzymes: zinc finger fusions to FokI cleavage domain. Proc Natl Acad Sci USA. 1996;93(3):1156–1160. DOI: 10.1073/pnas.93.3.1156</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S, et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature. 2005;435(7042):646–651. DOI: 10.1038/nature03556</mixed-citation><mixed-citation xml:lang="en">Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S, et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature. 2005;435(7042):646–651. DOI: 10.1038/nature03556</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Carroll D. Genome engineering: Zinc-finger nucleases and beyond. Nat Protoc. 2011;6(2): 239–254. DOI: 10.1534/genetics.111.131433</mixed-citation><mixed-citation xml:lang="en">Carroll D. Genome engineering: Zinc-finger nucleases and beyond. Nat Protoc. 2011;6(2): 239–254. DOI: 10.1534/genetics.111.131433</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Kim H, Kim JS. A guide to genome engineering with programmable nucleases. Nat Rev Genet. 2014;15(5):321–334. DOI: 10.1038/nrg3686</mixed-citation><mixed-citation xml:lang="en">Kim H, Kim JS. A guide to genome engineering with programmable nucleases. Nat Rev Genet. 2014;15(5):321–334. DOI: 10.1038/nrg3686</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science. 2009;326(5959):1509–1512. DOI: 10.1126/science.1178811</mixed-citation><mixed-citation xml:lang="en">Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science. 2009;326(5959):1509–1512. DOI: 10.1126/science.1178811</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Карагяур МН, Примак АЛ, Джауари СС, Бозов КД, Макусь ЮВ. Технологии редактирования генома и перспективы их применения в биомедицине. Регенерация органов и тканей. 2024;2(1):54–77. DOI: 10.60043/2949-5938-2024-1-54-77</mixed-citation><mixed-citation xml:lang="en">Карагяур МН, Примак АЛ, Джауари СС, Бозов КД, Макусь ЮВ. Технологии редактирования генома и перспективы их применения в биомедицине. Регенерация органов и тканей. 2024;2(1):54–77. DOI: 10.60043/2949-5938-2024-1-54-77</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Joung JK, Sander JD. TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol. 2013;14(1):49–55. DOI: 10.1038/nrm3486</mixed-citation><mixed-citation xml:lang="en">Joung JK, Sander JD. TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol. 2013;14(1):49–55. DOI: 10.1038/nrm3486</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Nemudryi AA, Valetdinova KR, Medvedev SP, Zakian SM. TALEN and CRISPR/Cas Genome Editing Systems: Tools of Discovery. Acta Naturae. 2014;6(3):19–40.</mixed-citation><mixed-citation xml:lang="en">Nemudryi AA, Valetdinova KR, Medvedev SP, Zakian SM. TALEN and CRISPR/Cas Genome Editing Systems: Tools of Discovery. Acta Naturae. 2014;6(3):19–40.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Doudna JA, Charpentier E. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014;346(6213):1258096. DOI: 10.1126/science.1258096</mixed-citation><mixed-citation xml:lang="en">Doudna JA, Charpentier E. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014;346(6213):1258096. DOI: 10.1126/science.1258096</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007;315(5819):1709–1712. DOI: 10.1126/science.1138140</mixed-citation><mixed-citation xml:lang="en">Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007;315(5819):1709–1712. DOI: 10.1126/science.1138140</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol. 1987;169(12):5429–5433. DOI: 10.1128/JB.169.12.5429-5433.1987</mixed-citation><mixed-citation xml:lang="en">Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol. 1987;169(12):5429–5433. DOI: 10.1128/JB.169.12.5429-5433.1987</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Mojica FJM, Ferrer C, Juez G, Rodríguez-Valera F. Long stretches of short tandem repeats are present in the largest replicons of the Archaea Haloferax mediterranei and Haloferax volcanii and could be involved in replicon partitioning. Mol Microbiol. 1995;17(1):85–93. DOI: 10.1111/j.1365-2958.1995.mmi_17010085.x</mixed-citation><mixed-citation xml:lang="en">Mojica FJM, Ferrer C, Juez G, Rodríguez-Valera F. Long stretches of short tandem repeats are present in the largest replicons of the Archaea Haloferax mediterranei and Haloferax volcanii and could be involved in replicon partitioning. Mol Microbiol. 1995;17(1):85–93. DOI: 10.1111/j.1365-2958.1995.mmi_17010085.x</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Jansen R, van Embden JDA, Gaastra W, Schouls LM. Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol. 2002;43(6):1565–1575. DOI: 10.1046/j.1365-2958.2002.02839.x</mixed-citation><mixed-citation xml:lang="en">Jansen R, van Embden JDA, Gaastra W, Schouls LM. Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol. 2002;43(6):1565–1575. DOI: 10.1046/j.1365-2958.2002.02839.x</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337(6096):816–821. DOI: 10.1126/science.1225829</mixed-citation><mixed-citation xml:lang="en">Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337(6096):816–821. DOI: 10.1126/science.1225829</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819–823. DOI: 10.1126/science.1231143</mixed-citation><mixed-citation xml:lang="en">Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819–823. DOI: 10.1126/science.1231143</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, et al. CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. N Engl J Med. 2021;384(3):252–260. DOI: 10.1056/NEJMoa2031054</mixed-citation><mixed-citation xml:lang="en">Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, et al. CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. N Engl J Med. 2021;384(3):252–260. DOI: 10.1056/NEJMoa2031054</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Nobel Foundation. The Nobel Prize in Chemistry 2020: Emmanuelle Charpentier and Jennifer A Doudna. NobelPrize.org. 2020.</mixed-citation><mixed-citation xml:lang="en">Nobel Foundation. The Nobel Prize in Chemistry 2020: Emmanuelle Charpentier and Jennifer A Doudna. NobelPrize.org. 2020.</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014;157(6):1262–1278. DOI: 10.1016/j.cell.2014.05.010</mixed-citation><mixed-citation xml:lang="en">Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014;157(6):1262–1278. DOI: 10.1016/j.cell.2014.05.010</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Joung JK, Sander JD. TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol. 2013;14(1):49–55. DOI: 10.1038/nrm3486</mixed-citation><mixed-citation xml:lang="en">Joung JK, Sander JD. TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol. 2013;14(1):49–55. DOI: 10.1038/nrm3486</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Adli M. The CRISPR tool kit for genome editing and beyond. Nat Commun. 2018;9:1911. DOI: 10.1038/s41467-018-04252-2</mixed-citation><mixed-citation xml:lang="en">Adli M. The CRISPR tool kit for genome editing and beyond. Nat Commun. 2018;9:1911. DOI: 10.1038/s41467-018-04252-2</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Dyikanov DT, Vasiluev PA, Rysenkova KD, Aleksandrushkina NA, Tyurin-Kuzmin PA, Kulebyakin KY, et al. Optimization of CRISPR/Cas9 technology to knock out genes of interest in aneuploid cell lines. Tissue Eng Part C Methods. 2019;25(3):168–175. DOI: 10.1089/ten.TEC.2018.0365</mixed-citation><mixed-citation xml:lang="en">Dyikanov DT, Vasiluev PA, Rysenkova KD, Aleksandrushkina NA, Tyurin-Kuzmin PA, Kulebyakin KY, et al. Optimization of CRISPR/Cas9 technology to knock out genes of interest in aneuploid cell lines. Tissue Eng Part C Methods. 2019;25(3):168–175. DOI: 10.1089/ten.TEC.2018.0365</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Anzalone AV, Randolph PB, Davis JR, Sousa AA, Koblan LW, Levy JM, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576(7785):149–157. DOI: 10.1038/s41586-019-1711-4</mixed-citation><mixed-citation xml:lang="en">Anzalone AV, Randolph PB, Davis JR, Sousa AA, Koblan LW, Levy JM, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576(7785):149–157. DOI: 10.1038/s41586-019-1711-4</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Hirano H, Gootenberg JS, Horii T, Abudayyeh OO, Kimura M, Hsu PD, et al. Structure and Engineering of Francisella novicida Cas9. Cell. 2016;164(5):950–961. DOI: 10.1016/j.cell.2016.01.039</mixed-citation><mixed-citation xml:lang="en">Hirano H, Gootenberg JS, Horii T, Abudayyeh OO, Kimura M, Hsu PD, et al. Structure and Engineering of Francisella novicida Cas9. Cell. 2016;164(5):950–961. DOI: 10.1016/j.cell.2016.01.039</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Faure G, Saito M, Wilkinson ME, Quinones-Olvera N, Xu P, Flam-Shepherd D, et al. TIGR-Tas: A family of modular RNA-guided DNA-targeting systems in prokaryotes and their viruses. Science. 2025;388(6746):eadv9789. DOI: 10.1126/science.adv9789</mixed-citation><mixed-citation xml:lang="en">Faure G, Saito M, Wilkinson ME, Quinones-Olvera N, Xu P, Flam-Shepherd D, et al. TIGR-Tas: A family of modular RNA-guided DNA-targeting systems in prokaryotes and their viruses. Science. 2025;388(6746):eadv9789. DOI: 10.1126/science.adv9789</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Kleinstiver BP, Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng Z, Joung JK. High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016;529(7587):490–495. DOI: 10.1038/nature16526</mixed-citation><mixed-citation xml:lang="en">Kleinstiver BP, Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng Z, Joung JK. High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016;529(7587):490–495. DOI: 10.1038/nature16526</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Cox DBT, Platt RJ, Zhang F. Therapeutic genome editing: prospects and challenges. Nat Med. 2015;21(2):121–131. DOI: 10.1038/nm.3793</mixed-citation><mixed-citation xml:lang="en">Cox DBT, Platt RJ, Zhang F. Therapeutic genome editing: prospects and challenges. Nat Med. 2015;21(2):121–131. DOI: 10.1038/nm.3793</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Gao C. Genome editing in crops: from bench to field. Nat Rev Mol Cell Biol. 2021;22(7):476–495. DOI: 10.1038/s41580-021-00409-y</mixed-citation><mixed-citation xml:lang="en">Gao C. Genome editing in crops: from bench to field. Nat Rev Mol Cell Biol. 2021;22(7):476–495. DOI: 10.1038/s41580-021-00409-y</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Hammond A, Galizi R, Kyrou K, Simoni A, Siniscalchi C, Katsanos D, et al. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol. 2016;34(1):78–83. DOI: 10.1038/nbt.3439</mixed-citation><mixed-citation xml:lang="en">Hammond A, Galizi R, Kyrou K, Simoni A, Siniscalchi C, Katsanos D, et al. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol. 2016;34(1):78–83. DOI: 10.1038/nbt.3439</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Dipaola MG, Fortuna C, Severini F, Bevivino G, Di Luca M, Nolan T, et al. Temporal and spatial profiling of Aedes albopictus immune responses to chikungunya virus infection. PLoS Negl Trop Dis. 2025;19(10):e0013588. DOI: 10.1371/journal.pntd.0013588</mixed-citation><mixed-citation xml:lang="en">Dipaola MG, Fortuna C, Severini F, Bevivino G, Di Luca M, Nolan T, et al. Temporal and spatial profiling of Aedes albopictus immune responses to chikungunya virus infection. PLoS Negl Trop Dis. 2025;19(10):e0013588. DOI: 10.1371/journal.pntd.0013588</mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Esvelt KM, Smidler AL, Catteruccia F, Church GM. Concerning RNA-guided gene drives for the alteration of wild populations. eLife. 2014;3:e03401. DOI: 10.7554/eLife.03401</mixed-citation><mixed-citation xml:lang="en">Esvelt KM, Smidler AL, Catteruccia F, Church GM. Concerning RNA-guided gene drives for the alteration of wild populations. eLife. 2014;3:e03401. DOI: 10.7554/eLife.03401</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru">Mazloum A, Karagyaur M, Chernyshev R, van Schalkwyk A, Jun M, Qiang F, Sprygin A. Post-genomic era in agriculture and veterinary science: successful and proposed application of genetic targeting technologies. Front Vet Sci. 2023;10:1180621. DOi: 10.3389/fvets.2023.1180621</mixed-citation><mixed-citation xml:lang="en">Mazloum A, Karagyaur M, Chernyshev R, van Schalkwyk A, Jun M, Qiang F, Sprygin A. Post-genomic era in agriculture and veterinary science: successful and proposed application of genetic targeting technologies. Front Vet Sci. 2023;10:1180621. DOi: 10.3389/fvets.2023.1180621</mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Petraitytė G, Preikšaitienė E, Mikštienė V. Genome Editing in Medicine: Tools and Challenges. Acta Med Litu. 2021;28(2):205–219. DOI: 10.15388/Amed.2021.28.2.8</mixed-citation><mixed-citation xml:lang="en">Petraitytė G, Preikšaitienė E, Mikštienė V. Genome Editing in Medicine: Tools and Challenges. Acta Med Litu. 2021;28(2):205–219. DOI: 10.15388/Amed.2021.28.2.8</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru">Niu D, Wei HJ, Lin L, George H, Wang T, Lee IH, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR–Cas9. Science. 2017;357(6357):1303–1307. DOI: 10.1126/science.aan4187</mixed-citation><mixed-citation xml:lang="en">Niu D, Wei HJ, Lin L, George H, Wang T, Lee IH, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR–Cas9. Science. 2017;357(6357):1303–1307. DOI: 10.1126/science.aan4187</mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">Stadtmauer EA, Fraietta JA, Davis MM, Cohen AD, Weber KL, Lancaster E, et al. CRISPR-engineered T cells in patients with refractory cancer. Science. 2020;367(6481):eaba7365. DOI: 10.1126/science.aba7365</mixed-citation><mixed-citation xml:lang="en">Stadtmauer EA, Fraietta JA, Davis MM, Cohen AD, Weber KL, Lancaster E, et al. CRISPR-engineered T cells in patients with refractory cancer. Science. 2020;367(6481):eaba7365. DOI: 10.1126/science.aba7365</mixed-citation></citation-alternatives></ref><ref id="cit72"><label>72</label><citation-alternatives><mixed-citation xml:lang="ru">Gillmore JD, Gane E, Taubel J, Kao J, Fontana M, Maitland ML, et al. CRISPR–Cas9 in vivo gene editing for transthyretin amyloidosis. N Engl J Med. 2021;385(6):493–502. DOI: 10.1056/NEJ-Moa2107454</mixed-citation><mixed-citation xml:lang="en">Gillmore JD, Gane E, Taubel J, Kao J, Fontana M, Maitland ML, et al. CRISPR–Cas9 in vivo gene editing for transthyretin amyloidosis. N Engl J Med. 2021;385(6):493–502. DOI: 10.1056/NEJ-Moa2107454</mixed-citation></citation-alternatives></ref><ref id="cit73"><label>73</label><citation-alternatives><mixed-citation xml:lang="ru">Intellia Therapeutics. NTLA-2001 phase III clinical data release. 2024.</mixed-citation><mixed-citation xml:lang="en">Intellia Therapeutics. NTLA-2001 phase III clinical data release. 2024.</mixed-citation></citation-alternatives></ref><ref id="cit74"><label>74</label><citation-alternatives><mixed-citation xml:lang="ru">Lanphier E, Urnov F, Haecker SE, Werner M, Smolenski J. Don’t edit the human germ line. Nature. 2015;519(7544):410–411. DOI: 10.1038/519410a</mixed-citation><mixed-citation xml:lang="en">Lanphier E, Urnov F, Haecker SE, Werner M, Smolenski J. Don’t edit the human germ line. Nature. 2015;519(7544):410–411. DOI: 10.1038/519410a</mixed-citation></citation-alternatives></ref><ref id="cit75"><label>75</label><citation-alternatives><mixed-citation xml:lang="ru">Baylis F. Altered inheritance: CRISPR and the ethics of human genome editing. CRISPR J. 2019;2(4):203–209. DOI: 10.4159/9780674241954</mixed-citation><mixed-citation xml:lang="en">Baylis F. Altered inheritance: CRISPR and the ethics of human genome editing. CRISPR J. 2019;2(4):203–209. DOI: 10.4159/9780674241954</mixed-citation></citation-alternatives></ref><ref id="cit76"><label>76</label><citation-alternatives><mixed-citation xml:lang="ru">Cornu TI, Mussolino C, Cathomen T. Refining strategies to translate genome editing to the clinic. Nat Med. 2017;23(4):415–423. DOI: 10.1038/nm.4313</mixed-citation><mixed-citation xml:lang="en">Cornu TI, Mussolino C, Cathomen T. Refining strategies to translate genome editing to the clinic. Nat Med. 2017;23(4):415–423. DOI: 10.1038/nm.4313</mixed-citation></citation-alternatives></ref><ref id="cit77"><label>77</label><citation-alternatives><mixed-citation xml:lang="ru">Baltimore D, Berg P, Botchan M, Carroll D, Charo RA, Church G, et al. A prudent path forward for genomic engineering and germline gene modification. Science. 2015;348(6230):36–38. DOI: 10.1126/science.aab1028</mixed-citation><mixed-citation xml:lang="en">Baltimore D, Berg P, Botchan M, Carroll D, Charo RA, Church G, et al. A prudent path forward for genomic engineering and germline gene modification. Science. 2015;348(6230):36–38. DOI: 10.1126/science.aab1028</mixed-citation></citation-alternatives></ref><ref id="cit78"><label>78</label><citation-alternatives><mixed-citation xml:lang="ru">Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, et al. Anti–BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019;380(18):1726–1737. DOI: 10.1056/NEJMoa1817226</mixed-citation><mixed-citation xml:lang="en">Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, et al. Anti–BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019;380(18):1726–1737. DOI: 10.1056/NEJMoa1817226</mixed-citation></citation-alternatives></ref><ref id="cit79"><label>79</label><citation-alternatives><mixed-citation xml:lang="ru">Kosicki M, Tomberg K, Bradley A. Repair of double-strand breaks induced by CRISPR– Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol. 2018;36(8):765–771. DOI: 10.1038/nbt.4192</mixed-citation><mixed-citation xml:lang="en">Kosicki M, Tomberg K, Bradley A. Repair of double-strand breaks induced by CRISPR– Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol. 2018;36(8):765–771. DOI: 10.1038/nbt.4192</mixed-citation></citation-alternatives></ref><ref id="cit80"><label>80</label><citation-alternatives><mixed-citation xml:lang="ru">Papathanasiou S, Markoulaki S, Blaine LJ, Leibowitz ML, Zhang CZ, Jaenisch R, et al. Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing. Nat Commun. 2021;12(1):5855. DOI: 10.1038/s41467-021-26097-y</mixed-citation><mixed-citation xml:lang="en">Papathanasiou S, Markoulaki S, Blaine LJ, Leibowitz ML, Zhang CZ, Jaenisch R, et al. Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing. Nat Commun. 2021;12(1):5855. DOI: 10.1038/s41467-021-26097-y</mixed-citation></citation-alternatives></ref><ref id="cit81"><label>81</label><citation-alternatives><mixed-citation xml:lang="ru">Uddin F, Rudin CM, Sen T. CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future. Front Oncol. 2020;10:1387. DOI: 10.3389/fonc.2020.01387</mixed-citation><mixed-citation xml:lang="en">Uddin F, Rudin CM, Sen T. CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future. Front Oncol. 2020;10:1387. DOI: 10.3389/fonc.2020.01387</mixed-citation></citation-alternatives></ref><ref id="cit82"><label>82</label><citation-alternatives><mixed-citation xml:lang="ru">Rehman SU, Abbas GH. CRISPR/CAS9-based gene editing in cancer therapy: A systematic review and meta-analysis on current status and future directions. Medicine (Baltimore). 2026;105(2):e47114. DOI: 10.1097/MD.0000000000047114</mixed-citation><mixed-citation xml:lang="en">Rehman SU, Abbas GH. CRISPR/CAS9-based gene editing in cancer therapy: A systematic review and meta-analysis on current status and future directions. Medicine (Baltimore). 2026;105(2):e47114. DOI: 10.1097/MD.0000000000047114</mixed-citation></citation-alternatives></ref><ref id="cit83"><label>83</label><citation-alternatives><mixed-citation xml:lang="ru">Doudna JA. The promise and challenge of therapeutic genome editing. Nature. 2020; 578(7794):229–236. DOI: 10.1038/s41586-020-1978-5</mixed-citation><mixed-citation xml:lang="en">Doudna JA. The promise and challenge of therapeutic genome editing. Nature. 2020; 578(7794):229–236. DOI: 10.1038/s41586-020-1978-5</mixed-citation></citation-alternatives></ref><ref id="cit84"><label>84</label><citation-alternatives><mixed-citation xml:lang="ru">National Academies of Sciences, Engineering, and Medicine. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: National Academies Press; 2017. DOI: 10.17226/24623</mixed-citation><mixed-citation xml:lang="en">National Academies of Sciences, Engineering, and Medicine. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: National Academies Press; 2017. DOI: 10.17226/24623</mixed-citation></citation-alternatives></ref><ref id="cit85"><label>85</label><citation-alternatives><mixed-citation xml:lang="ru">Karagyaur MN, Efimenko AYu, Makarevich PI, Vasiluev PA, Akopyan ZhA, Bryzgalina EV, et al. Ethical and legal aspects of using genome-editing technologies in medicine (review). Contemporary Technologies in Medicine. 2019;11(3):117–135. DOI: 10.17691/stm2019.11.3.16</mixed-citation><mixed-citation xml:lang="en">Karagyaur MN, Efimenko AYu, Makarevich PI, Vasiluev PA, Akopyan ZhA, Bryzgalina EV, et al. Ethical and legal aspects of using genome-editing technologies in medicine (review). Contemporary Technologies in Medicine. 2019;11(3):117–135. DOI: 10.17691/stm2019.11.3.16</mixed-citation></citation-alternatives></ref><ref id="cit86"><label>86</label><citation-alternatives><mixed-citation xml:lang="ru">Bredenoord AL, Schneider M, van Delden JJM. Ethical issues in genome editing: CRISPR– Cas9 and beyond. EMBO Rep. 2021;22(1):e52018. DOI: 10.15252/embr.202052018</mixed-citation><mixed-citation xml:lang="en">Bredenoord AL, Schneider M, van Delden JJM. Ethical issues in genome editing: CRISPR– Cas9 and beyond. EMBO Rep. 2021;22(1):e52018. DOI: 10.15252/embr.202052018</mixed-citation></citation-alternatives></ref><ref id="cit87"><label>87</label><citation-alternatives><mixed-citation xml:lang="ru">Bosley KS, Botchan M, Bredenoord AL, Carroll D, Charo RA, Charpentier E, et al. CRISPR germline engineering: the community speaks. Nat Biotechnol. 2015;33(5):478–486. DOI: 10.1038/nbt.3227</mixed-citation><mixed-citation xml:lang="en">Bosley KS, Botchan M, Bredenoord AL, Carroll D, Charo RA, Charpentier E, et al. CRISPR germline engineering: the community speaks. Nat Biotechnol. 2015;33(5):478–486. DOI: 10.1038/nbt.3227</mixed-citation></citation-alternatives></ref><ref id="cit88"><label>88</label><citation-alternatives><mixed-citation xml:lang="ru">Wang H, Lu H, Lei YS, Gong CY, Chen Z, Luan YQ, et al., Development of a Self-Restricting CRISPR-Cas9 System to Reduce Off-Target Effects. Mol Ther Methods Clin Dev. 2020;18:390-401. DOI: 10.1016/j.omtm.2020.06.012</mixed-citation><mixed-citation xml:lang="en">Wang H, Lu H, Lei YS, Gong CY, Chen Z, Luan YQ, et al., Development of a Self-Restricting CRISPR-Cas9 System to Reduce Off-Target Effects. Mol Ther Methods Clin Dev. 2020;18:390-401. DOI: 10.1016/j.omtm.2020.06.012</mixed-citation></citation-alternatives></ref><ref id="cit89"><label>89</label><citation-alternatives><mixed-citation xml:lang="ru">Xu CL, Ruan MZC, Mahajan VB, Tsang SH. Viral Delivery Systems for CRISPR. Viruses. 2019;4;11(1):28. DOI: 10.3390/v11010028.</mixed-citation><mixed-citation xml:lang="en">Xu CL, Ruan MZC, Mahajan VB, Tsang SH. Viral Delivery Systems for CRISPR. Viruses. 2019;4;11(1):28. DOI: 10.3390/v11010028.</mixed-citation></citation-alternatives></ref><ref id="cit90"><label>90</label><citation-alternatives><mixed-citation xml:lang="ru">Park SH, Lee CM, Dever DP, Davis TH, Camarena J, Srifa W, et al. Highly efficient editing of the β-globin gene in patient-derived hematopoietic stem and progenitor cells to treat sickle cell disease. Nucleic Acids Res. 2019;47(15):7955–7972. DOI: 10.1093/nar/gkz475</mixed-citation><mixed-citation xml:lang="en">Park SH, Lee CM, Dever DP, Davis TH, Camarena J, Srifa W, et al. Highly efficient editing of the β-globin gene in patient-derived hematopoietic stem and progenitor cells to treat sickle cell disease. Nucleic Acids Res. 2019;47(15):7955–7972. DOI: 10.1093/nar/gkz475</mixed-citation></citation-alternatives></ref><ref id="cit91"><label>91</label><citation-alternatives><mixed-citation xml:lang="ru">Hoban MD, Cost GJ, Mendel MC, Romero Z, Kaufman ML, Joglekar AV, et al. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells. Blood. 2016;127(7):839–848. DOI: 10.1182/blood-2015-11-679381</mixed-citation><mixed-citation xml:lang="en">Hoban MD, Cost GJ, Mendel MC, Romero Z, Kaufman ML, Joglekar AV, et al. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells. Blood. 2016;127(7):839–848. DOI: 10.1182/blood-2015-11-679381</mixed-citation></citation-alternatives></ref><ref id="cit92"><label>92</label><citation-alternatives><mixed-citation xml:lang="ru">Bischof J, Hierl M, Koller U. Emerging Gene Therapeutics for Epidermolysis Bullosa under Development. Int J Mol Sci. 2024;25(4):2243. DOI: 10.3390/ijms25042243</mixed-citation><mixed-citation xml:lang="en">Bischof J, Hierl M, Koller U. Emerging Gene Therapeutics for Epidermolysis Bullosa under Development. Int J Mol Sci. 2024;25(4):2243. DOI: 10.3390/ijms25042243</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
