Катионные липосомы как средства доставки нуклеиновых кислот

Цели. Генная терапия основана на введении генетического материала в клетки, ткани или органы с целью лечения наследственных или приобретенных заболеваний. Ключевым фактором успеха генной терапии является развитие систем доставки, способных эффективно переносить генетический материал к месту их терапевтического действия, не вызывая каких-либо связанных с ними побочных эффектов. За последнее десять лет много усилий было направлено на создание более эффективных и биосовместимых векторов, способных переносить нуклеиновые кислоты в клетки, не вызывая иммунного ответа. Катионные липосомы являются одним из самых универсальных инструментов для доставки нуклеиновых кислот в клетки, однако применение липосом для целей генной терапии ограничено неспецифичностью такой доставки. Это связано с наличием различных биологических барьеров на пути комплекса липосом с нуклеиновыми кислотами; например, с нестабильностью в биологических жидкостях; взаимодействиями с белками сыворотки крови, плазматической и ядерной мембранами; а также с эндосомной деградацией. В этом обзоре обобщены результаты исследований за последние годы по разработкам катионных липосом, эффективных in vitro и in vivo. Особое внимание уделено отдельным структурным элементам катионных липосом, определяющим эффективность трансфекции и цитотоксичность. Целью данного обзора являлось теоретическое обоснование выбора катионных липосом, наиболее перспективных для доставки нуклеиновых кислот в эукариотические клетки, а также изучение влияния состава катионных липидов на эффективность трансфекции in vitro.

Результаты. В результате проведенного анализа литературы можно утверждать, что одними из наиболее перспективных систем доставки нуклеиновых кислот являются катионные липиды на основе холестерина и спермина с добавлением липида-хелпера DOPE. Кроме того, было установлено, что варьирование состава катионных липосом, соотношения катионных липидов и нуклеиновых кислот, а также размера и дзета-потенциала липосом оказывают значительное влияние на эффективность трансфекции.

Выводы. Дальнейшие исследования в данном направлении должны включать в себя оптимизацию условий получения катионных липосом с учетом установленных закономерностей, а также физико-химических свойств. Необходимо исследовать возможности повышения эффективности доставки нуклеиновых кислот путем поиска оптимальных структур катионных липосом, определения соотношения компонентов липоплексов и изучения свойств и эффективности доставки многокомпонентных липосом in vitro.

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