Сенсорные системы, 2020, T. 34, № 3, стр. 188-200

Три тактики генной терапии двух врожденных заболеваний сетчатки. Обзор

Е. М. Максимова 1*, П. В. Максимов 1

1 Федеральное государственное бюджетное учреждение науки Институт проблем передачи информации им. А.А. Харкевича РАН
127051 Москва, Большой Каретный пер., 19, Россия

* E-mail: maximova@iitp.ru

Поступила в редакцию 02.03.2020
После доработки 06.04.2020
Принята к публикации 27.04.2020

Аннотация

Приведены литературные данные о генетических причинах двух врожденных заболеваний сетчатки – LCA2 и LCA10 (детская прогрессирующая слепота) и о современных способах их лечения. Причиной LCA2 является разрыв зрительного цикла из-за дефекта гена RPE65, экспрессирующегося в клетках пигментного эпителия сетчатки (RPE). Для лечения разработана и применяется усиливающая генная терапия (augmentation therapy): векторное субретинальное введение нормального гена RPE65. LCA10 – цилиопатия, вызванная мутацией гена CEP290, экспрессирующегося в основании связывающей реснички (CC) фоторецептора. Для лечения применяется “антисмысловая” терапия, устраняющая интронную (дефектную) мутацию в молекуле пре-мРНК в процессе синтеза белка CEP290. Рассказано о проекте “BRILLIANCE” – первом испытании прямого редактирования генома методом CRISPR/Cas9 прямо в теле пациента LCA10, анонсированном в номере Nature за 2020 г.

Ключевые слова: сетчатка, пигментный эпителий, RPE65, CEP290, LCA2, LCA10, генная терапия, цилия, редактирование генома, CRISPR/Cas9, сепофарсен

DOI: 10.31857/S0235009220030051

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Дополнительные материалы отсутствуют.