dCasMINI-mediated therapy rescues photoreceptors degeneration in a mouse model of retinitis pigmentosa

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2024-12-18 DOI:10.1126/sciadv.adn7540

Qing Wang, Xiaoshu Xu, Siyu Chen, Rui Lu, Liang Li, Chien-Hui Lo, Zhiquan Liu, Ke Ning, Tingting Li, Tia J. Kowal, Biao Wang, Mary E. Hartnett, Sui Wang, Lei S. Qi, Yang Sun

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引用次数: 0

Abstract

Retinitis pigmentosa (RP) is characterized by degeneration of rod and cone photoreceptors that progresses to irreversible blindness. Now, there are no mutation-agnostic approaches to treat RP. Here, we utilized a single adeno-associated virus (AAV)–based CRISPR activation system to activate phosphodiesterase 6B (Pde6b) to mitigate the severe degeneration in Pde6a nmf363 mice. We demonstrate that transcriptional activation of Pde6b can rescue the loss of Pde6a , with preservation of retinal structure, restoration of electroretinography responses, and improvement of visual function as assessed by optokinetic response and looming-induced escape behaviors. These findings demonstrate the therapeutic potential of a dCasMINI-mediated activation strategy that provides a mutation-independent treatment for retinal degeneration. This study offers a promising therapeutic approach for RP and potentially other forms of genetic diseases.

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.