Современные генетические технологии для терапии синдрома Штаргардта. Часть 1. Невирусные методы доставки терапевтических конструкций

Болезнь Штаргардта (STGD1) является наиболее распространенной наследственной макулярной дистрофией. Это аутосомно- рецессивное заболевание, вызываемое патогенными вариантами гена ABCA4, который кодирует трансмембранный белок се- мейства АТР-связывающих кассетных транспортеров, локализованный в наружных сегментах фоторецепторов и необходимый для рециркуляции ретиналя — основной части зрительного пигмента родопсина. Дисфункция транспортера ABCA4 приводит к накоплению токсичных производных витамина А в клетках пигментного эпителия сетчатки с последующей дегенерацией фото- рецепторов. В последние годы фундаментальные и трансляционные исследования молекулярной патофизиологии наследствен- ных заболеваний сетчатки, в том числе болезни Штаргардта, значительно углубили понимание их механизмов, что стимулиро- вало активное развитие новых терапевтических стратегий. Целью данного обзора является описание современных подходов, направленных на коррекцию генетического дефекта в STGD1, а также анализ их преимуществ и ограничений с точки зрения возможного использования в клинической практике. В первой части обзора рассматриваются последние достижения в области применения малых молекул, а также невирусные технологии генной терапии в контексте лечения болезни Штаргардта.

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