мРНК-терапия: проблемы и перспективы применения в нефрологии

Успешное применение вакцин на основе мессенджерных РНК (мРНК) с целью профилактики инфекции COVID-19 привлекло внимание научной общественности к потенциальному клиническому использованию этих молекул в качестве инновационных и альтернативных терапевтических подходов в различных областях медицины. В качестве терапевтических средств мРНК могут быть выгодны благодаря своим уникальным биологическим свойствам – способности нацеливаться практически на любой генетический компонент клетки, кодировать любые белки и пептиды без необходимости их переноса в ядра клеток-мишеней. Кроме того, эти молекулы могут быть быстро разработаны/произведены и клинически испытаны. После оптимизации химического состава РНК и системы ее доставки стоимость разработки новых вариантов этих лекарств для вновь выбранных клинических заболеваний значительно снижается. Однако, несмотря на потенциальную ценность в качестве нового и высокоэффективного терапевтического инструмента против ряда заболеваний почек, сложная архитектура почек и неспособность наночастиц, содержащих олигонуклеотиды, преодолеть интегральный барьер гломерулярной фильтрации в значительной степени снизили их потенциальное применение в нефрологии. Тем не менее, ожидается, что в ближайшие несколько лет технические усовершенствования мРНК, повышающие эффективность трансляции, модулирующие врожденную и адаптивную иммуногенность и увеличивающие их избирательную доставку к месту действия, позволят преодолеть эти ограничения и возможности терапии, направленной на почки, значительно расширятся. Это тем более важно, если учесть, что хронической болезнью почек в той или иной степени страдают более 10 % взрослого населения в мире, а по прогнозам, к 2040 году она станет пятой основной причиной смерти. Цель данного мини-обзора – обобщить основные преимущества терапии на основе мРНК и проиллюстрировать потенциальные будущие направления и проблемы этой многообещающей технологии для широкого терапевтического использования в нефрологии.

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