Механизмы специфичности системы CRISPR/Cas9 в геномном редактировании

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Аннотация

Не так давно открытая система CRISPR/Cas9, основанная на действии комплементарно адресуемых нуклеаз и изначально предназначенная для защиты бактерий от чужеродных генетических элементов, стала удобным инструментом в руках ученых для манипуляции геномами живых клеток. Технология геномного редактирования CRISPR/Cas9 вышла за пределы лаборатории и уже находит применение в биотехнологии и сельском хозяйстве. Однако использование этого метода для редактирования клеток человека в медицинских целях ограничено внеадресной активностью системы CRISPR/Cas9, которая может привести к появлению онкогенных мутаций. В связи с этим ведутся активные исследования с целью разработки вариантов системы CRISPR/Cas9 с повышенной точностью. В обзоре освещены механизмы точного и ошибочного действия рибонуклеопротеина Cas9, природные и искусственно созданные варианты РНК-адресуемых нуклеаз, способы модуляции специфичности за счет модификации направляющей РНК и другие подходы к увеличению точности системы CRISPR/Cas9 в геномном редактировании.

Об авторах

Л. М. Кулишова

Институт химической биологии и фундаментальной медицины, Сибирское отделение Российской академии наук

Email: dzharkov@niboch.nsc.ru
Россия, 630090, Новосибирск

И. П. Вохтанцев

Институт химической биологии и фундаментальной медицины, Сибирское отделение Российской академии наук

Email: dzharkov@niboch.nsc.ru
Россия, 630090, Новосибирск

Д. В. Ким

Институт химической биологии и фундаментальной медицины, Сибирское отделение Российской академии наук; Новосибирский государственный университет

Email: dzharkov@niboch.nsc.ru
Россия, 630090, Новосибирск; Россия, 630090, Новосибирск

Д. О. Жарков

Институт химической биологии и фундаментальной медицины, Сибирское отделение Российской академии наук; Новосибирский государственный университет

Автор, ответственный за переписку.
Email: dzharkov@niboch.nsc.ru
Россия, 630090, Новосибирск; Россия, 630090, Новосибирск

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