vestibИзвестия Национальной академии наук Беларуси. Серия биологических наукProceedings of the National Academy of Sciences of Belarus, Biological Series1029-89402524-230XThe Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1029-8940-2018-63-1-113-125vestib-353Research ArticleОБЗОРЫREVIEWSИНДУЦИРОВАННЫЕ ПЛЮРИПОТЕНТНЫЕ СТВОЛОВЫЕ КЛЕТКИ, CRISPR-CAS9 (КРИСПЕР) СИСТЕМА РЕДАКТИРОВАНИЯ ГЕНОМОВ И ПЕРСПЕКТИВЫ РЕШЕНИЯ ПРОБЛЕМЫ ГЕННОЙ ТЕРАПИИ НАСЛЕДСТВЕННЫХ ЗАБОЛЕВАНИЙ ЧЕЛОВЕКАINDUCED PLURIPOTENT STEM CELLS, CRISPR-CAS9 (KRISPER) GENOME EDITING SYSTEM AND PERSPECTIVES OF SOLVING THE PROBLEM OF GENE THERAPY OF HUMAN HEREDITARY DISEASESВолотовскийИ. Д.VolotovskiI. D.

академик, д-р биол. наук, профессор, заведующий лабораторией

Academician, D. Sc. (Biol.), Professor, Head of the Department

volotovski@yahoo.comПолешкоА. Г.PoleshkoA. G.

канд. биол. наук, науч. сотрудник

Ph. D. (Biol.), Researcher

renovacio888@yandex.ruИнститут биофизики и клеточной инженерии НАН Беларуси, МинскInstitute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus, Minsk201804042018631113125Copyright © Волотовский И.Д., Полешко А.Г., 20182018Волотовский И.Д., Полешко А.Г.Volotovski I.D., Poleshko A.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestibio.belnauka.by/jour/article/view/353

В данном обзоре рассматриваются две оригинальные технологии в области клеточной биологии, перевернувшие наши представления о том, что происходит в процессе эмбрионального развития с белками, из которых построен организм человека. Эти технологии, появившиеся совсем недавно, привлекли самое пристальное внимание биологов и послужили мощным толчком для развития новых исследований, направленных на целевое изменение структуры и функционирования генетического аппарата клетки. Указанные технологии связаны с мезенхимальными стволовыми клетками и преследуют решение задач, стоящих перед генной терапией наследственных заболеваний человека. Первая технология использует индуцированные плюрипотентные стволовые клетки, продукт обычных соматических клеток, которым придаются свойства эмбриональных стволовых клеток, т. е. способность превращаться в любую специализированную клетку организма. Вторая технология предлагает достаточно прос- той и выполнимый в условиях лаборатории прием редактирования геномов клеток, заключающийся в проведении на уровне генома генно-инженерных манипуляций, заканчивающихся устранением мутации, элиминацией дефектных генов или вставкой новых генов, лишенных каких-либо ошибок.

The given review considers the two original technologies in the field of cell biology turning our views over the processes taking place during embryogenesis with proteins of which our organism is built. They appeared more recently, attracted the closest attention of the biologists and have served as a powerful impetus for development of new researches aimed at a targeted change in the structure and function of cell genetic apparatus. These technologies are directly tied to mesenchymal stem cells and pursue the solution of the tasks facing gene therapy of human hereditary diseases. The first one considers induced pluripotent stem cells, e.g. giving somatic cells the ability to turn into each specialized cells of organism. The second technology offers quite simple and feasible in conditions of biological laboratory approach of editing cell genome. It consists in carrying out at the level of genome genetic engineering manipulations terminating in the elimination of mutations from genes, defected genes or insertion into genome of new gene devoted of any errors.

 

редактирование геномаиндуцированные плюрипотентные стволовые клеткисистема CRISPR-Cas9genome editinginduced pluripotent stem cellssystem CRISPR-Cas95ReferencesPera, M. F. Human pluripotent stem cells: a progress report / M. F. Pera // Current Opinion in Genetics & Development. – 2001. – Vol. 11, N 5. – P. 595–599.Pera M. F. Human pluripotent stem cells: a progress report. Current opinion in genetics and development, 2001, vol. 11, no. 5, pp. 559–599. DOI: 10.1016/s0959-437x(00)00238-0Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the same coin / P. M. M. Matin [et al.] // Biochemical Society Transactions. – 2005. – Vol. 33, N 6. – P. 1526–1530.Matin M. M., Andrews P. W., Bahrami A. R., Damjanov I., Gokhale P., Draper J. S. Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the same coin. Biochemical Society Transactions, 2005, vol. 33, no. 6, pp. 1526–1530. DOI: 10.1042/bst20051526Takahashi, K. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors / K. Takahashi, S. Yamanaka // Cell. – 2006. – Vol. 126, N 4. – P. 663–676.Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, vol. 126, no. 4, pp. 663–676. DOI: 10.1016/j.cell.2006.07.024Induced pluripotent stem cells generated without viral integration / M. Stadtfeld [et al.] // Science. – 2008. – Vol. 322, N 5903. – P. 945–949.Stadtfeld M., Nagaya M., Utikal J., Weir G., Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science, 2008, vol. 322, no. 5903, pp. 945–949. DOI: 10.1126/science.1162494Identification of potential pluripotency determinants for human embryonic stem cells following proteomic analysis of human and mouse fibroblast conditioned media / A. B. J. Prowse [et al.] // J. Proteome Research. – 2007. – Vol. 6, N 9. – P. 3796–3807.Prowse A. B. J., McQuade L. R., Bryant K. J., Marcal H., Gray P. P. Identification of potential pluripotency determinants for human embryonic stem cells following proteomic analysis of human and mouse fibroblast conditioned media. Journal of Proteome Research, 2007, vol. 6, no. 9, pp. 3796–3807. DOI: 10.1021/pr0702262Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3 / H. Yuan [et al.] // Genes and Development. – 1995. – Vol. 9, N 21. – P. 2635–2645.Yuan H., Corbi N., Basilico C., Dailey L. Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes and Development, 1995, vol. 9, no. 21, pp. 2635–2645. DOI: 10.1101/gad.9.21.2635A bivalent chromatin structure marks key developmental genes in embryonic stem cells / B. E. Bernstein [et al.] // Cell. – 2006. – Vol. 125, N 2. – P. 315–326.Bernstein B. E., Mikkelsen T. S., Xie X., Kamal M., Huebert D. J., Cuff J., Fry B., Meissner A., Wernig M., Plath K., Jaenisch R., Wagschal A., Feil R., Schreiber S. L., Lander E. S. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell, 2006, vol. 125, no. 2, pp. 315–326. DOI: 10.1016/j.cell.2006.02.041Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4 / J. Nichols [et al.] // Cell. – 1998. – Vol. 95, N 3. – P. 379–391.Nichols J., Zevnik B., Anastassiadis K., Niwa H., Klewe-Nebenius D., Chambers I., Schöler H., Smith A. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell, 1998, vol. 95, no. 3, pp. 379–391. DOI: 10.1016/s0092-8674(00)81769-9Dang, D. T. The biology of the mammalian Krüppel–like family of transcription factors / D. T. Dang, J. Pevsner, V. W. Yang // The Intern. J. of Biochemistry and Cell Biology. – 2000. – Vol. 32, N 11–12. – P. 1103–1121.Dang D. T., Pevsner J., Yang V. W. The biology of the mammalian Krüppel-like family of transcription factors. The Interna- tional Journal of Biochemistry and Cell Biology, 2000, vol. 32, no. 11–12, pp. 1103–1121. DOI: 10.1016/s1357-2725(00)00059-5The c-Myc target gene network / C. V. Dang [et al.] // Seminars in Cancer Biology. – 2006. – Vol. 16, N 4. – P. 253–264.Dang C. V., O’Donnell K. A., Zeller K. I., Nguyen T., Osthus R. C., Li F. The c-Myc target gene network. Seminars in Cancer Biology, 2006, vol. 16, no. 4, pp. 253–264. DOI: 10.1016/j.semcancer.2006.07.014Analysis of genomic targets reveals complex functions of MYC / J. H. Patel [et al.] // Nature Rev. Cancer. – 2004. – Vol. 4, N 7. – P. 562–568.Patel J. H., Loboda A. P., Showe M. K., Showe L. C., McMahon S. B. Analysis of genomic targets reveals complex functions of MYC. Nature Reviews. Cancer, 2004, vol. 4, no. 7, pp. 562–568. DOI: 10.1038/nrc1393Widespread microRNA repression by Myc contributes to tumorigenesis / T.-C. Chang [et al.] // Nature Genetics. – 2008. – Vol. 40, N 1. – P. 43–50.Chang T.-C., Yu D., Lee Y.-S., Wentzel E. A., Arking D. E., West K. M., Dang C. V., Thomas-Tikhonenko A., Mendell J. T. Widespread microRNA repression by Myc contributes to tumorigenesis. Nature Genetics, 2008, vol. 40, no. 1, pp. 43–50. DOI: 10.1038/ng.2007.30Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts / M. Nakagawa [et al.] // Nature Biotechnology. – 2008. – Vol. 26, N 1. – P. 101–106.Nakagawa M., Koyanagi M., Tanabe K., Takahashi K., Ichisaka T., Aoi T., Okita K., Mochiduki Y., Takizawa N., Yamanaka S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature Biotechnology, 2008, vol. 26, no. 1, pp. 101–106. DOI: 10.1038/nbt1374Induced pluripotent stem cell lines derived from human somatic cells / J. Yu [et al.] // Science. – 2007. – Vol. 318, N 5858. – P. 1917–1920.Yu J., Vodyanik M. A., Smuga-Otto K., Antosiewicz-Bourget J., Frane J. L., Tian S., Nie J., Jonsdottir G. A., Ruotti V., Stewart R., Slukvin I. I., Thomson J. A. Induced pluripotent stem cell lines derived from human somatic cells. Science, 2007, vol. 318, no. 5858, pp. 1917–1920. DOI: 10.1126/science.1151526Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET / T. Matsui [et al.] // Nature. – 2010. – Vol. 464, N 7290. – P. 927–931.Matsui T., Leung D., Miyashita H., Maksakova I. A., Miyachi H., Kimura H., Tachibana M., Lorincz M. C., Shinkai Y. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature, 2010, vol. 464, no. 7290, pp. 927–931. DOI: 10.1038/nature08858A high-efficiency system for the generation and study of human induced pluripotent stem cells / N. Maherali [et al.] // Cell Stem Cell. – 2008. – Vol. 3, N 3. – P. 340–345.Maherali N., Ahfeldt T., Rigamonti A., Utikal J., Cowan C., Hochedlinger K. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell, 2008, vol. 3, no. 3, pp. 340–345. DOI: 10.1016/j.stem.2008.08.003Deterministic direct reprogramming of somatic cells to pluripotency / Y. Rais [et al.] // Nature. – 2013. – Vol. 502, N 7469. – P. 65–70.Rais Y., Zviran A., Geula S., Gafni O., Chomsky E., Viukov S., Mansour A. A., Caspi I., Krupalnik V., Zerbib M., Maza I., Mor N., Baran D., Weinberger L., Jaitin D. A., Lara-Astiaso D., Blecher-Gonen R., Shipony Z., Mukamel Z., Hagai T., Gilad S., Amann-Zalcenstein D., Tanay A., Amit I., Novershtern N., Hanna J. H. Deterministic direct reprogramming of somatic cells to pluripotency. Nature, 2013, vol. 502, no. 7469, pp. 65–70. DOI: 10.1038/nature12587Kaji, K. Mbd3, a component of the NuRD co–repressor complex, is required for development of pluripotent cells / K. Kaji, J. Nichols, B. Hendrich // Development. – 2007. – Vol. 134, N 6. – P. 1123–1132.Kaji K., Nichols J., Hendrich B. Mbd3, a component of the NuRD co-repressor complex, is required for development of pluripotent cells. Development, 2007, vol. 134, no. 6, pp. 1123–1132. DOI: 10.1242/dev.02802Multiplex genome engineering using CRISPR/Cas9 systems / L. Cong [et al.] // Science. – 2013. – Vol. 339, N 6121. – P. 819–823.Cong L., Ran F. A., Cox D., Lin S., Barretto R., Habib N., Hsu P. D., Wu X., Jiang W., Marraffini L. A., Zhang F. Multiplex genome engineering using CRISPR/Cas9 systems. Science, 2013, vol. 339, no. 6121, pp. 819–823. DOI: 10.1126/science.1231143Capecchi, M. R. Gene targeting in mice: functional analisys of mammalian genome for the twenty-first century / M. R. Capecchi // Nature Rev. Genetics. – 2005. – Vol. 6, N 6. – P. 507–512.Capecchi M. R. Gene targeting in mice: functional analisys of mammalian genome for the twenty-first century. Nature Reviews Genetics, 2005, vol. 6, no. 6, pp. 507–512. DOI: 10.1038/nrg1619Potent a specific genetic interference by double–stranded RNAi Caenoharbditis elegans / A. Fire [et al.] // Nature. – 1998. – Vol. 391, N 6669. – P. 806–811.Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., Mello C. C. Potent a specific genetic interference by double-stranded RNAi Caenoharbditis elegans. Nature, 1998, vol. 391, no. 6669, pp. 806–811. DOI: 10.1038/35888Analysis of gene function in somatic mammalian cells using small interfering RNAs / S. M. Elbashir [et al.] // Methods. – 2002. – Vol. 26, N 2. – P. 199–213.Elbashir S. M., Harborth J., Weber K., Tuschl T. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods, 2002, vol. 26, no. 2, pp. 199–213. DOI: 10.1016/s1046-2023(02)00023-3Analysis of mammalian gene function using small inreference RNAs / J. Martinez [et al.] // Nucleic Acids Symposium Series. – 2003. – Vol. 3, N 1. – P. 333.Martinez J., Patkaniowska A., Elbashir S. M., Harborth J., Hossbach M., Urlaub H., Meyer J., Weber K., Vandenburgh K., Manninga H., Scaringe S. A., Luehrmann R., Tuschl T. Analysis of mammalian gene function using small inreference RNAs. Nucleic Acids Research. Supplement, 2003, vol. 3, no. 1, p. 333. DOI: 10.1093/nass/3.1.333Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing / N. Alic [et al.] // PloS One. – 2012. – Vol. 7, N 9. – P. e45376.Alic N., Hoddinott M. P., Foley A., Slack C., Piper M. D., Partridge L. Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing. PloS One, 2012, vol. 7, no. 9, pp. e45376. DOI: 10.1371/journal.pone.0045367Theoretic applicability of antisense–mediated exon skipping for Duchenne muscular dsptrophy / A. Aartsma-Rus [et al.] // Human Mutation. – 2009. – Vol. 30, N 3. – P. 293–299.Aartsma-Rus A., Fokkema I., Verschuuren J., Ginjaar I., van Deutekom J., van Ommen G. J., den Dunnen J. T. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dsptrophy. Human Mutation, 2009, vol. 30, no. 3, pp. 293–299. DOI: 10.1002/humu.20918Porteus, M. H. Mammalian gene targeting with designed zinc finger nucleases / M. H. Porteus // Molecular Therapy. – 2006. – Vol. 13, N 2. – P. 438–446.Porteus M. H. Mammalian gene targeting with designed zinc finger nucleases. Molecular Therapy, 2006, vol. 13, no. 2, pp. 438–446. DOI: 10.1016/j.ymthe.2005.08.003A novel TALE nuclease acagffold enable high genome editing activity in combination with low toxicity / C. Mussollino [et al.] // Nycleic Acids Research. – 2011. – Vol. 39, N 21. – P. 9283–9293.Mussolino C., Morbitzer R., Lütge F., Dannemann N., Lahaye T., Cathomen T. A novel TALE nuclease acagffold enable high genome editing activity in combination with low toxicity. Nucleic Acids Research, 2011, vol. 39, no. 21, pp. 9283–9293. DOI: 10.1093/nar/gkr597A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity / M. Jinek [et al.] // Science. – 2012. – Vol. 337, N 6096. – P. 816–821.Jinek M., Chylinski K., Fonfara I., Hauer M., Doudna J. A., Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, 2012, vol. 337, no. 6096, pp. 816–821. DOI: 10.1126/science.1225829Harnessing the CRISPR/Cas9 system to disrupt latent HIV–1 provirus / H. Ebina [et al.] // Sci. Rep. – 2013. – N 3. – Art. nr 2510.Ebina H., Misawa N., Kanemura Y., Koyanagi Y. Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus. Scientific Reports, 2013, no. 3, art. nr 2510. DOI: 10.1038/srep02510Валетдинова, К. Р. Применение системы CRISPR/Cas9 для создания и исследования клеточных моделей наследственных заболеваний человека / К. Р. Валетдинова // Гены и клетки. – 2016. – Т. 11, № 2. – С. 10–20.Valetdinova K. R. Application of CRISPR/Cas9 system for developing and studying cellular models of inherited disease. Geny i kletki [Genes and Cells], 2016, vol. 11, no. 2, pp. 10–20 (in Russian).

The authors declare that there are no conflicts of interest present.