Разработка препаратов, полученных путем редактирования генома: регуляторная практика

Новейшим подходом в генной терапии является использование систем редактирования генома соматических клеток для лечения пациентов с наследственными моногенными, онкологическими заболеваниями и инфицированных вирусом иммунодефицита человека. Редактирование генома позволяет изменить дефектный ген или провести его полное удаление с помощью систем «нуклеазы с цинковыми пальцами» (ZFN), «эффекторные нуклеазы, подобные активаторам транскрипции» (TALEN) и «короткие палиндромные повторы, регулярно расположенные группами с CRISPR-ассоциированным белком 9» (CRISPR-Cas9).

Цель работы: анализ мирового опыта и нормативных требований к разработке препаратов, полученных с использованием технологии редактирования генома постнатальных соматических клеток.

В работе описаны принципы методов редактирования генов CRISPR, ZFN, TALEN, сравнение преимуществ и недостатков каждого подхода. Разработка, производство и оценка препаратов, полученных с использованием технологий редактирования генома, так же как и этические аспекты их применения, требуют особого подхода со стороны регуляторных и законодательных органов. В настоящее время требования и рекомендации к разработке таких препаратов ограничиваются преимущественно необходимостью оценки возникновения нецелевых эффектов и рисков отложенных по времени нежелательных явлений; возможностью адаптации дизайна клинических исследований в аспекте применения суррогатных конечных точек, исключения из исследований здоровых добровольцев и групп сравнения, выбора начальной дозы для клинических исследований на основе научных данных. Кроме того, должны быть разработаны регуляторные подходы для государственной регистрации препаратов на основе систем редактирования генома.

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