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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">vestim</journal-id><journal-title-group><journal-title xml:lang="ru">Известия Национальной  академии наук Беларуси. Серия медицинских наук</journal-title><trans-title-group xml:lang="en"><trans-title>Proceedings of the National Academy of Sciences of Belarus, Medical series</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1814-6023</issn><issn pub-type="epub">2524-2350</issn><publisher><publisher-name>The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"</publisher-name></publisher></journal-meta><article-meta><article-id custom-type="elpub" pub-id-type="custom">vestim-393</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</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group></article-categories><title-group><article-title>ИММУННАЯ СИСТЕМА ПРОКАРИОТ: МОЛЕКУЛЯРНЫЕ МЕХАНИЗМЫ, ПРИМЕНЕНИЕ В МИКРОБИОЛОГИИ</article-title><trans-title-group xml:lang="en"><trans-title>PROCARIOTIC IMMUNE SYSTEM: MOLECULAR MECHANISMS, APPLICATION IN MICROBIOLOGY</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>Хархаль</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Kharkhal</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>мл. науч. сотрудник</p></bio><bio xml:lang="en"><p>Junior researcher</p></bio><email xlink:type="simple">anna-madlen69@yandex.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>Титов</surname><given-names>Л. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Titov</surname><given-names>L. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>член-корреспондент, иностранный член РАМН, д-р мед. наук, профессор, заведующий лабораторией</p></bio><bio xml:lang="en"><p>Corresponding Member, Foreign Member of the RAMS, D. Sc. (Med.), Head of the Laboratory</p></bio><email xlink:type="simple">leonidtitov@tut.by</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Республиканский научно-практический центр эпидемиологии и микробиологии</institution></aff><aff xml:lang="en"><institution>Republican Research and Practical Center for Epidemiology and Microbiology</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2017</year></pub-date><pub-date pub-type="epub"><day>08</day><month>10</month><year>2017</year></pub-date><volume>0</volume><issue>3</issue><fpage>121</fpage><lpage>128</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Хархаль А.Н., Титов Л.П., 2017</copyright-statement><copyright-year>2017</copyright-year><copyright-holder xml:lang="ru">Хархаль А.Н., Титов Л.П.</copyright-holder><copyright-holder xml:lang="en">Kharkhal A.N., Titov L.P.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" 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://vestimed.belnauka.by/jour/article/view/393">https://vestimed.belnauka.by/jour/article/view/393</self-uri><abstract><p>Система CRISPR/Cas за короткие сроки завоевала популярность среди ученых различных областей медицинских, биологических и химических наук. Данная система, кассета которой состоит из кодирующих Cas-белки генов лидерной последовательности, спейсеров и палиндромов, используется для защиты собственного генома от чужеродного генетического материала прокариоты. Сas-белки являются ключевым звеном, без которых эта система не способна выполнять свои функции. При взаимодействии с чужеродной ДНК система CRISPR/Cas проходит три этапа: иммунизацию, экспрессию и интерференцию. Иммунизация происходит при первичном контакте клетки с чужеродной ДНК с запоминанием информации об инвазивном агенте. При повторной встрече отмечается образование белкового комплекса и разрушение чужеродной ДНК. Различия в механизме процесса зависят от класса и типа системы CRISPR/Cas. Различают 2 класса системы CRISPR/Cas, которые разделены на 5 типов и 16 подтипов. Для поиска CRISPR у бактерий используются биоинформационные методы, разработаны специализированные программы. В связи с высокой эффективностью работы и простотой сборки отдельных компонентов в лабораторных условиях CRISPR/Cas стали применять для решения широкого круга задач в микробиологии, генетике, молекулярной эпидемиологии, генной инженерии, прикладной медицине и фармакологии для редактирования геномов, контроля экспрессии генов, лечения и моделирования патологических процессов, типирования микроорганизмов, определения филогенетических отношений между ними и др. Для редактирования генома эукариот хорошо зарекомендовала себя система CRISPR/Cas9 N. meningitidis. Однако эксперименты в области редактирования человеческого генома сопряжены с биоэтическими проблемами.</p><p> </p></abstract><trans-abstract xml:lang="en"><p>During a short time, the CRISPR/Cas system has gained popularity among scientists in various fields of medicine, biology, and chemistry. Prokaryotes use the CRISPR/Cas system to protect their own genome from foreign genetic material, the cassette of which consists of Cas-protein coding genes, leader sequence, speisers and palindromes. Cas-proteins are the main thing without which the CRISPR/Cas system cannot work. While interacting with foreign DNA, the CRISPR/Cas system passes 3 stages: immunization, expression, and interference. Immunization takes place during the first bacterial contact with foreign DNA collecting information about an invasive agent. The next meeting reveals the protein complex creation and the foreign DNA destruction. The differences in the mechanisms of action depend on the system class and type. There are 2 classes of the CRISPR/Cas system separating into 5 types and 16 subtypes. Bioinformation methods are used to find the CRISPR/Cas system in a bacterial cell. Due to the high efficiency and the easy individual component assembly, scientists quickly learned how to benefit from the CRISPR/Cas system, applying it for a wide range of tasks. The CRISPR/Cas system is used in microbiology, genetics, molecular epidemiology, gene engineering, applied medicine, and pharmacology for genome editing, gene expression control, pathological process treatment and modeling, microorganism typing, determination of phylogenetic relationships of microorganisms and so on. The CRISPR/Cas system of N. meningitidis can successfully edit eucariotic genome. But experiments with human genome are connected with biomedical ethics.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>система CRISPR/Cas</kwd><kwd>иммунизация</kwd><kwd>экспрессия</kwd><kwd>интерференция</kwd><kwd>редактирование генома</kwd></kwd-group><kwd-group xml:lang="en"><kwd>CRISPR/Cas system</kwd><kwd>immunization</kwd><kwd>expression</kwd><kwd>interference</kwd><kwd>genome editing</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Титов, Л. П. Класификация, номенклатура и эволюция значимых для медицины бактерий / Л. П. Титов // Мед. журн. – 2006. – № 1. – С. 13–18.</mixed-citation><mixed-citation xml:lang="en">Titov L. P. Classiﬁcation, nomenclature and evolution medically signiﬁcant bacteria. Meditsinskii zhurnal [Medical Journal], 2006, pp. 13–19. (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Эволюция мира микробов и ее медицинское значение / Л. П. Титов [и др.] // Здравоохранение. – 2002. – № 8. – С. 30–35.</mixed-citation><mixed-citation xml:lang="en">Titov L. P., Votyakov V. I., Kozhemiakin A. K., Mosina L. I. Bacterial evolution and it’s medical value. Zdravoohranenie [Health Care], 2002, no. 8, pp. 30–35. (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Nucleotide sequence of the iap gene, responsible for alkaline phosphatase sozyme conversion in Escherichia coli, and identiﬁcation of the gene product / Y. Ishino [et al.] // J. of Bacteriol. – 1987. – Vol. 169, N 12. – P. 5429–5433.</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. Journal of Bacteriology, 1987, vol. 169, no. 12, pp. 5429–5433.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Identiﬁcation of genes that are associated with DNA repeats in prokaryotes / R. Jansen [et al.] // Mol. Microbiol. – 2002. – Vol. 43, N 6. – P. 1565–1575.</mixed-citation><mixed-citation xml:lang="en">Jansen R., Embden J. D., Gaastra W., Schouls L. M. Identiﬁcation of genes that are associated with DNA repeats in prokaryotes. Molecular Microbiology, 2002, vol. 43, no. 6, pp. 1565–1575.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action / K. S. Makarova [et al.] // Biology Direct. – 2006. – Vol. 1. – P. 7.</mixed-citation><mixed-citation xml:lang="en">Makarova K. S., Grishin N. V., Shabalina S. A., Wolf Y. I., Koonin E. V. A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biology Direct, 2006, vol. 1, p. 7.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Sontheimer, E. J. The bacterial origins of the CRISPR genome-editing revolution / E. J. Sontheimer, R. Barrangou // Human Gene Therapy. – 2015. – Vol. 26, N 7. – P. 413–424.</mixed-citation><mixed-citation xml:lang="en">Sontheimer E. J., Barrangou R. The Bacterial Origins of the CRISPR Genome-Editing Revolution. Human Gene Therapy, 2015, vol. 26, no. 7, pp. 413–424. doi: 10.1089/hum.2015.091.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Rationally engineered Cas9 nucleases with improved speciﬁcity / I. M. Slaymaker [et al.] // Science. – 2016. – Vol. 351 (6268). – P. 84–88.</mixed-citation><mixed-citation xml:lang="en">Slaymaker I. M., Gao L., Zetsche B., Scott D. A., Zhang F. Rationally engineered Cas9 nucleases with improved speciﬁcity. Science, 2016, vol. 351 (6268), pp. 84–88. doi: 10.1126/science. aad5227.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Barrangou, R. The roles of CRISPR-Cas systems in adaptive immunity and beyond / R. Barrangou // Curr. Opin. in Immunol. – 2015. – Vol. 32. – P. 36–41.</mixed-citation><mixed-citation xml:lang="en">Barrangou R. The roles of CRISPR-Cas systems in adaptive immunity and beyond. Current Opinion in Immunology, 2015, vol. 32, pp. 36–41. doi: 10.1016/j. coi.2014.12.008.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Шашникова, А. В. Строение и функциональная роль CRISPR-системы бактерий / А. В. Шашникова, А. А. Горяев, Н. И. Смирнова // Проблемы особо опасных инфекций. – 2011. – № 2 (108). – С. 49–52.</mixed-citation><mixed-citation xml:lang="en">Shashnikova A. V., Goriaev A. A., Smirnova N. I. Structure and functional role of bacterial CRISPR system. Problemy osobo opasnykh infektsii [Problems of Especially Dangerous Infections], 2011, no. 2 (108), pp. 49–52. (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Bacterial CRISPR: accomplishments and prospects / J. M. Peters [et al.] // Curr. Opin. in Microbiol. – 2015. – Vol. 27. – P. 121–126.</mixed-citation><mixed-citation xml:lang="en">Peters J. M., Silvis M. R., Zhao D., Hawkins J. S., Gross C. A., Qi L. S. Bacterial CRISPR: accomplishments and prospects. Current Opinion in Microbiology, 2015, vol. 27, pp. 121–126.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex / C. R. Hale [et al.] // Cell. – 2009. – Vol. 139, N 5. – P. 945–956.</mixed-citation><mixed-citation xml:lang="en">Hale C. R., Zhao P., Olson S., Duff M. O., Graveley B. R., Wells L., Terns R. M., Terns M. P. RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex. Cell, 2009, vol. 139, no. 5, pp. 945–956.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">MacSyFinder: a program to mine genomes for molecular systems with an application to CRISPR-Cas systems / S. S. Abby [et al.] // PLOS ONE. – 2014. – Vol. 9, N 10. – P. 1–9.</mixed-citation><mixed-citation xml:lang="en">Abby S. S., Neron B., Menager H., Touchon M., Rocha E. P. MacSyFinder: a program to mine genomes for molecular systems with an application to CRISPR-Cas systems. PLOS ONE, 2014, vol. 9, no. 10, pp. 1–9.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Использование биоинформационных программных методов для поиска CRISPR/Cas систем в геномах штаммов Staphylococcus aureus / А. Ю. Борисенко [и др.] // Сибир. мед. журн. (Иркутск). – 2015. – Т. 133, № 2. – С. 71–74.</mixed-citation><mixed-citation xml:lang="en">Borisenko A. Iu., Dzhioev Iu. P., Paramonov A. I., Bukin Iu. S., Stepanenko L. A., Kolbaseeva O. V., Zlobin I. V. The use of bioinformatics software methods for search CRISPR/Cas systems in genomes of the strains of Staphylococcus aureus. Sibirskii meditsinskii zhurnal (Irkutsk) [Siberian Medical Journal (Irkutsk)], 2015, vol. 133, no. 2, pp. 71–74. (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Savitskaya, E. E. Diversity of CRISPR-Cas-mediated mechanisms of adaptive immunity in prokaryotes and their application in biotechnology / E. E. Savitskaya, O. S. Musharova, K. V. Severinov // Biochemistry. – 2016. – Vol. 81, N 7. – P. 653–661.</mixed-citation><mixed-citation xml:lang="en">Savitskaya E. E., Musharova O. S., Severinov K. V. Diversity of CRISPR-Cas-mediated mechanisms of adaptive immunity in prokaryotes and their application in biotechnology. Biochemistry, 2016, vol. 81, no. 7, pp. 653–661.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Lee, C. The Neisseria meningitidis CRISPR-Cas9 System enables speciﬁc genome editing in mammalian cells / C. Lee, T. Cradick, G. Bao // Mol. Therapy. – 2016. – Vol. 24, N 3. – P. 645–654.</mixed-citation><mixed-citation xml:lang="en">Lee C., Cradick T., Bao G. The Neisseria meningitidis CRISPR-Cas9 System Enables Speciﬁc Genome Editing in Mammalian Cells. Molecular Therapy, 2016, vol. 24, no. 3, pp. 645–654.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Barrangou, R. Diversity of CRISPR-Cas immune systems and molecular machines / R. Barrangou // Genome Biol. – 2015. – Vol. 16. – P. 247–257.</mixed-citation><mixed-citation xml:lang="en">Barrangou R. Diversity of CRISPR-Cas immune systems and molecular machines. Genome Biology, 2015, vol. 16, pp. 247–257.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">The diversity-generating beneﬁts of a prokaryotic adaptive immune system / S. van Houte [et al.] // Nature. – 2016. – Vol. 532 (7599). – P. 385–388.</mixed-citation><mixed-citation xml:lang="en">Van Houte S., Ekroth A. K., Broniewski, Chabas H., Ashby B., Bondy-Denomy J., Gandon S., Boots M., Paterson S., Buckling A., Westra E. R. The diversity-generating beneﬁts of a prokaryotic adaptive immune system. Nature, 2016, vol. 532 (7599), pp. 385–388. doi: 10.1038/nature17436.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Programmable RNA recognition and cleavage by CRISPR/Cas9 / M. R. O’Connell [et al.] // Nature. – 2014. – Vol. 516 (7530). – P. 263–266.</mixed-citation><mixed-citation xml:lang="en">O’Connell M. R., Oakes B. L., Sternberg S. H., East-Seletsky A., Kaplan M., Doudna J. A. Programmable RNA recognition and cleavage by CRISPR/Cas9. Nature, 2014, vol. 516, no. 7530, pp. 263–266.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Makarova, K. S. Annotation and classiﬁcation of CRISPR-Cas systems / K. S. Makarova, E. V. Koonin // Methods in Mol. Biol. – 2015. – Vol. 1311. – P. 47–75.</mixed-citation><mixed-citation xml:lang="en">Makarova K. S., Koonin E. V. Annotation and Classiﬁcation of CRISPR-Cas Systems. Methods in Molecular Biology, 2015, vol. 1311, pp. 47–75.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">An updated evolutionary classiﬁcation of CRISPR-Cas systems / K. S. Makarova [et al.] // Nature Reviews: Microbiology. – 2015. – Vol. 13, N 11. – P. 722–736.</mixed-citation><mixed-citation xml:lang="en">Makarova K. S., Wolf Y. I., Alkhnbashi O. S., Costa F., Shah S. A., Saunders S. J., Barrangou R., Brouns S. J., Charpentier E., Haft D. H., Horvath P., Moineau S., Mojica F. J., Terns R. M., Terns M. P., White M. F., Yakunin A. F., Garrett R. A., van der Oost J., Backofen R., Koonin E. V. An updated evolutionary classiﬁcation of CRISPR-Cas systems. Nature Reviews: Microbiology, 2015, vol. 13, no. 11, pp. 722–736.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins / J. Bondy-Denomy [et al.] // Nature. – 2015. – Vol. 526 (7571). – P. 136–139.</mixed-citation><mixed-citation xml:lang="en">Bondy-Denomy J., Garcia B., Strum S., Du M., Rollins M. F., Hidalgo-Reyes Y., Wiedenheft B., Maxwell K. L., Davidson A. R. Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins. Nature, 2015, vol. 526 (7571), pp. 136–139.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Hilton, I. B. Genetic engineering: Chemical control for CRISPR editing / I. B. Hilton, C. A. Gersbach // Nature Chem. Biol. – 2017. – Vol. 13. – P. 2–3.</mixed-citation><mixed-citation xml:lang="en">Hilton I. B., Gersbach C. A. Genetic engineering: Chemical control for CRISPR editing. Nature Chemical Biology, 2017, vol. 13, pp. 2–3.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Sashital, D. G. Mechanism of foreign DNA selection in a bacterial adaptive immune system / D. G. Sashital, B. Wiedenheft, J. A. Doudna // Cell. – 2012. – Vol. 46. – P. 606–615.</mixed-citation><mixed-citation xml:lang="en">Sashital D. G., Wiedenheft B., Doudna J. A. Mechanism of foreign DNA selection in a bacterial adaptive immune system. Cell, 2012, vol. 46, pp. 606–615.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Sangal, V. Novel conﬁgurations of type I and II CRISPR-Cas systems in Corynebacterium diphteriae / V. Sangal, P. C. Fineran, P. A. Hoskisson // Microbiology. – 2013. – Vol. 159. – P. 2118–2126.</mixed-citation><mixed-citation xml:lang="en">Sangal V., Fineran P. C., Hoskisson P. A. Novel conﬁgurations of type I and II CRISPR-Cas systems in Corynebacterium diphteriae. Microbiology, 2013, no. 159, pp. 2118–2126.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Classiﬁcation and evolution of type II CRISPR-Cas systems / K. Chylinski [et al.] // Nucl. Acids Res. – 2014. – Vol. 42, N 10. – P. 6091–6105.</mixed-citation><mixed-citation xml:lang="en">Chylinski K., Makarova K. S., Charpentier E., Koonin E. V. Classiﬁcation and evolution of type II CRISPR-Cas systems. Nucleic Acids Research, 2014, vol. 42, no. 10, pp. 6091–6105.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems / I. Fonfara [et al.] // Nucl. Acids Res. – 2014. – Vol. 42, N 4. – P. 2577–2590.</mixed-citation><mixed-citation xml:lang="en">Fonfara I., Le Rhun A., Chylinski K., Makarova K. S., Lйcrivain A. L., Bzdrenga J., Koonin E. V., Charpentier E. Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems. Nucleic Acids Research, 2014, vol. 42, no. 4, pp. 2577–2590.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Васильева, Е. А. Применение системы направленного геномного редактирования CRISPR/Cas к плюрипотентным стволовым клеткам / Е. А. Васильева, Д. Мелино, Н. А. Барлев // Цитология. – 2015. – Т. 57, № 1. – С. 19–30.</mixed-citation><mixed-citation xml:lang="en">Vasil’eva E. A., Melino D., Barlev N. A. CRISPR/Cas system for genome editing in pluripotent stem cells. Tsitologiia [Cytology], 2015, vol. 57, no. 1, pp. 19–30. (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Efﬁcient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis / Z. Hou [et al.] // Proc. Natl. Acad. Sci. USA. – 2013. – Vol. 110. – P. 15644–15649.</mixed-citation><mixed-citation xml:lang="en">Hou Z., Zhang Y., Propson N. E., Howden S. E., Chu L. F., Sontheimer E. J., Sontheimer B., Thomson J. A. Efﬁcient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proceedings of the National Academy of Sciences of the United States of America, 2013, no. 110, pp. 15644–15649.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Merkett, S. Site-speciﬁc genome engineering in human pluripotent stem cells / S. Merkett, U. Martin // Intern. J. of Mol. Sci. – 2016. – Vol. 17 (1000). – P. 1–11.</mixed-citation><mixed-citation xml:lang="en">Merkett S., Martin U. Site-speciﬁc genome engineering in human pluripotent stem cells. International Journal of Molecular Sciences, 2016, vol. 17 (1000), pp. 1–11.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Samson, J. E. The CRISPR-Cas immune system and genetic transfers: reaching an equilibrium / J. E. Samson, A. H. Magadan, S. Moineau // Microbiol. Spectrum. – 2015. – Vol. 3, N 1. – P. 209–218.</mixed-citation><mixed-citation xml:lang="en">Samson J. E., Magadan A. H., Moineau S. The CRISPR-Cas immune system and genetic transfers: reaching an equilibrium. Microbiology Spectrum, 2015, vol. 3, no. 1, pp. 209–218.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Precision medicine: genetic repair of retinitis pigmentosa in patient-derived stem cells / A. G. Bassuk [et al.] // Sci. Reports. – 2016. – Vol. 6.</mixed-citation><mixed-citation xml:lang="en">Bassuk A. G., Zheng A., Li Y., Tsang S. H., Mahajan V. B. Precision medicine: genetic repair of retinitis pigmentosa in patient-derived stem cells. Scientiﬁc Reports, 2016, vol. 6, p. 19969. doi:10.1038/srep19969.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Naïve induced pluripotent stem cells generated from β-thalassemia ﬁbroblasts allow efﬁcient gene correction with CRISPR/Cas9 / Y. Yang [et al.] // Stem Cells Translational Medicine. – 2016. – Vol. 5, N 1. – P. 8–19.</mixed-citation><mixed-citation xml:lang="en">Yang Y., Zhang X., Yi L., Hou Z., Chen J., Kou X., Zhao Y., Wang H., Sun X. F., Jiang C., Wang Y., Gao S. Naïve induced pluripotent stem cells generated from β-thalassemia ﬁbroblasts allow efﬁcient gene correction with CRISPR/Cas9. Stem Cells Translational Medicine, 2016, vol. 5, no. 1, pp. 8–19.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Goodman, M. A. CRISPR/Cas9 in allergic and immunologic diseases / M. A. Goodman, P. Malik, M. E. Rothenberg // Expert Rev. of Clin. Immunol. – 2016. – P. 1–5.</mixed-citation><mixed-citation xml:lang="en">Goodman M. A., Malik P., Rothenberg M. E. CRISPR/Cas9 in allergic and immunologic diseases. Expert Review of Clinical Immunology, 2016, pp. 1–5.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">The application of CRISPR/Cas9 genome editing technology in cancer research / D. Wang [et al.] // Yi Chuan. – 2016. – Vol. 38, N 1. – P. 1–8.</mixed-citation><mixed-citation xml:lang="en">Wang D., Ma Ning, Hui Yang, Gao Xu. The application of CRISPR/Cas9 genome editing technology in cancer research. Yi Chuan, 2016, vol. 38, no. 1, pp. 1–8. doi: 10.16288/j. yczz.15–252.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Li, Y. The potential application and challenge of powerful CRISPR/Cas9 system in cardiovascular research / Y. Li, Y. H. Song, B. Liu, X. Y. Yu // Intern. J. of Cardiol. – 2016. – Vol. 9. – P. 191–193.</mixed-citation><mixed-citation xml:lang="en">Li Y., Song Y. H., Liu B., Yu X. Y. The potential application and challenge of powerful CRISPR/Cas9 system in cardiovascular research. International Journal of Cardiology, 2016, vol. 9, pp. 191–193.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids / B. S. Freedman [et al.] // Nature Communications. – 2015. – Vol. 6. – P. 1–13.</mixed-citation><mixed-citation xml:lang="en">Freedman B. S., Brooks C. R., Lam A. Q., Fu H., Morizane R., Agrawal V., Saad A. F., Li M. K., Hughes M. R., Werff R. V., Peters D. T., Lu J., Baccei A., Siedlecki A. M., Valerius M. T., Musunuru K., McNagny K. M., Steinman T., Zhou J., Lerou P. H., Bonventre J. V. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nature Communications, 2015, vol. 6, pp. 1–13. doi: 10.1038/ncomms9715.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype / H. Yin [et al.] // Nature Biotechnol. – 2014. – Vol. 32, N 6. – P. 551–553.</mixed-citation><mixed-citation xml:lang="en">Yin H., Xue W., Chen S., Bogorad R. L., Benedetti E., Grompe M., Koteliansky V., Sharp P. A., Jacks T., Anderson D. G. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nature Biotechnology, 2014, vol. 32, no. 6, pp. 551–553. doi: 10.1038/nbt.2884.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Niemann, H. The production of multi-transgenic pigs: update and perspectives for xenotransplantation / H. Niemann, B. Petersen // Transgenic Res. – 2016. – P. 1–14.</mixed-citation><mixed-citation xml:lang="en">Niemann H., Petersen B. The production of multi-transgenic pigs: update and perspectives for xenotransplantation. Transgenic Research, 2016, pp. 1–14.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Schiml, S. Revolutionizing plant biology: multiple ways of genome engineering by CRISPR/Cas / S. Schiml, H. Puchta // Plant Methods. – 2016. – Vol. 12, N 8. – P. 1–9.</mixed-citation><mixed-citation xml:lang="en">Schiml S., Puchta H. Revolutionizing plant biology: multiple ways of genome engineering by CRISPR/Cas. Plant Methods, 2016, vol. 12, no. 8, pp. 1–9.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Schwartz, M. L. SapTrap, a toolkit for high-throughput CRISPR/Cas9 gene modiﬁcation in Caenorhabditis elegans / M. L. Schwarz, E. M. Jorgensen // Genetics. – 2016. – Vol. 202, N 4. – P. 1277–1288.</mixed-citation><mixed-citation xml:lang="en">Schwartz M. L., Jorgensen E. M. SapTrap, a toolkit for high-throughput CRISPR/Cas9 gene modiﬁcation in Caenorhabditis elegans. Genetics, 2016, vol. 202, no. 4, pp. 1277–1288. doi: 10.1534/genetics.115.184275.</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>
