Knockout and Replacement Gene Surgery to Treat Rhodopsin-Mediated Autosomal Dominant Retinitis Pigmentosa.
Xuehan SunChen LiangYangcan ChenTongtong CuiJiabao HanMoyu DaiYing ZhangQi ZhouWei LiPublished in: Human gene therapy (2024)
Mutations in the rhodopsin ( RHO ) gene are the predominant causes of autosomal dominant retinitis pigmentosa (adRP). Given the diverse gain-of-function mutations, therapeutic strategies targeting specific sequences face significant challenges. Here, we provide a universal approach to conquer this problem: we have devised a CRISPR-Cas12i-based, mutation-independent gene knockout and replacement compound therapy carried by a dual AAV2/8 system. In this study, we successfully delayed the progression of retinal degeneration in the classic mouse disease model Rho P23H , and also Rho P347S , a new native mouse mutation model we developed. Our research expands the horizon of potential options for future treatments of RHO-mediated adRP.
Keyphrases
- crispr cas
- protein kinase
- copy number
- genome wide
- smooth muscle
- genome wide identification
- minimally invasive
- genome editing
- optical coherence tomography
- gene expression
- stem cells
- dna methylation
- current status
- mesenchymal stem cells
- risk assessment
- genome wide analysis
- bone marrow
- coronary artery disease
- gene therapy
- wild type
- replacement therapy