Proceedings of the National Academy of Sciences of the United States of America · 2022
Targeting ON-bipolar cells by AAV gene therapy stably reverses LRIT3-congenital stationary night blindness.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Miyadera Keiko, Santana Evelyn, Roszak Karolina, Iffrig Sommer, Visel Meike, Iwabe Simone, Boyd Ryan F, Bartoe Joshua T, Sato Yu, Gray Alexa, Ripolles-Garcia Ana, Dufour Valérie L, Byrne Leah C, Flannery John G, Beltran William A, Aguirre Gustavo D
Аннотация
SignificanceCanine models of inherited retinal diseases have helped advance adeno-associated virus (AAV)-based gene therapies targeting specific cells in the outer retina for treating blinding diseases in patients. However, therapeutic targeting of diseases such as congenital stationary night blindness (CSNB) that exhibit defects in ON-bipolar cells (ON-BCs) of the midretina remains underdeveloped. Using a leucine-rich repeat, immunoglobulin-like and transmembrane domain 3 (LRIT3) mutant canine model of CSNB exhibiting ON-BC dysfunction, we tested the ability of cell-specific AAV capsids and promotors to specifically target ON-BCs for gene delivery. Subretinal injection of one vector demonstrated safety and efficacy with robust and stable rescue of electroretinography signals and night vision up to 1 y, paving the way for clinical trials in patients.