Применение антисмысловых молекул для коррекции нарушений сплайсинга в терапии наследственных заболеваний
https://doi.org/10.25557/2073-7998.2023.02.3-17
Аннотация
Сплайсинг – сложно регулируемый этап экспрессии генов, в котором задействованы множественные цис-элементы, представленные консенсусными последовательностями пре-мРНК, а также трансэлементы – белки и рибонуклеопротеиновые комплексы. Описано множество патогенных генетических вариантов, являющихся причиной нарушения сплайсинга, и ряд исследований направлен на создание эффективных способов их коррекции. Последние работы, посвященные пониманию регуляции сплайсинга, позволили разработать несколько инструментов его коррекции для терапии наследственных заболеваний. В данном обзоре описан опыт применения конструкций на основе антисмысловых молекул in vitro и in vivo, учитывающих особенности механизма нарушения сплайсинга и задействованные элементы его регуляции, рассматриваются преимущества и недостатки применения с целью коррекции сплайсинга антисмысловых олигонуклеотидов, модифицированных малых ядерных рибонуклеопротеинов, системы модификации пре-мРНК на основе механизма транс-сплайсинга, а также способы их доставки в клетки с использованием вирусных векторов.
При поддержке: Работа выполнена в рамках государственного задания Минобрнауки России для ФГБНУ «МГНЦ»
Об авторах
А. С. Галушкин
ФГБНУ «Медико-генетический научный центр им. акад. Н. П. Бочкова»
Россия
Россия
Артур Сергеевич Галушкин
115522
ул. Москворечье, д. 1
Москва
А. Ю. Некрасов
ФГБНУ «Медико-генетический научный центр им. акад. Н. П. Бочкова»
Россия
Россия
115522
ул. Москворечье, д. 1
Москва
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Рецензия
Для цитирования:
Галушкин А.С., Некрасов А.Ю. Применение антисмысловых молекул для коррекции нарушений сплайсинга в терапии наследственных заболеваний. Медицинская генетика. 2023;22(2):3-17. https://doi.org/10.25557/2073-7998.2023.02.3-17
For citation:
Galushkin A.S., Nekrasov A.Yu. The use of antisense molecules for splicing modulation as a treatment for genetic disorders. Medical Genetics. 2023;22(2):3-17. (In Russ.) https://doi.org/10.25557/2073-7998.2023.02.3-17
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