Невирусные системы внутриклеточной доставки инструментов редактирования генома

Последние десятилетия отмечены интенсивным развитием технологий и систем редактирования генов, которое вывело генную инженерию на новый уровень. Важным звеном этих технологий является специфичная и эффективная доставка компонентов таких систем в клетки-мишени. Традиционные векторы не всегда подходят для этой цели ввиду ограниченного объема полезной нагрузки, рисков, связанных с канцерогенезом и иммуногенностью, токсичности, необходимости высокой степени очистки и оценки качества полученных вирусных носителей, а также возможности встраивания вируса в геном хозяина, что может приводить к сверхэкспрессии компонентов вируса и проблемам с безопасностью. Это обусловливает актуальность поиска новых средств внутриклеточной доставки белков и нуклеиновых кислот. В данной работе приведен обзор абиотических векторов и систем доставки инструментов для редактирования генома, включая липосомы и твердые липидные наночастицы, мембранные везикулы иной природы, пептиды, проникающие в клетки, мицеллы, дендримеры, углеродные нанотрубки, неорганические, полимерные и другие наночастицы, металл-органические каркасные полимеры. Рассмотрены их преимущества, недостатки и предпочтительные области применения, а также возможность их использования для доставки систем редактирования генов. Особое внимание уделено металл-органическим каркасным полимерам и их потенциалу в качестве средств избирательной внутриклеточной доставки белков и полинуклеотидов. Сделан вывод о том, что дальнейшее развитие таких векторов и технологий на их основе может привести к появлению безопасных и эффективных систем доставки, способных длительно циркулировать в крови и распознавать клетки-мишени, обеспечивая адресное высвобождение полезной нагрузки в неизменном состоянии и тем самым улучшая результаты редактирования генов.

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