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利用核酶缺乏的CasX来预防病理性血管生成

Haote Han¹, Yanhui Yang², Yunjuan Jiao^3,4

¹Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou 310000, People's Republic of China.

Molecular therapy. Nucleic acids

|September 4, 2023

概括

克里斯普尔基因编辑有效地阻断了视网膜细胞中的酸酸3-激酶三角酶 (PI3Kδ) 表达. 这种方法在小鼠模型中防止了病态视网膜血管生成,提供了一种新的治疗策略.

科学领域:

分子生物学分子生物学
基因治疗基因治疗
眼科医生眼科眼科

背景情况:

基因编辑为人类疾病提供了新的治疗策略.
酸胺3-酶三角酶 (PI3Kδ) 的抑制抑制了视网膜血管生成.
氧气诱导的视网膜病变是病理性血管生成的小鼠模型.

研究的目的:

开发和评估一种由腺相关病毒 (AAV) 介导的CRISPR干扰系统,以阻止PI3Kδ的表达.
评估该系统在预防病态视网膜血管生成中的有效性.

主要方法:

一个由腺相关病毒 (AAV) 介导的CRISPR/缺核酶 (d) CasX与Krueppel关联盒 (KRAB) 系统融合的系统被设计为准Pik3cd.
该CRISPR/dCasX-KRAB系统被包装成一个单一的AAV向量.
再组合AAV血清型1 (rAAV1) 用于转导血管内皮细胞,并在氧气诱导视网膜病变的小鼠模型中进行了静脉内注射.

主要成果:

在体外,CRISPR/dCasX-KRAB系统有效地阻断了p110δ的表达 (81.2%±6.5%).
在体内注射rAAV1-CRISPR/dCasX-KRAB可以防止视网膜p110δ表达 (32.1%±5.3%).
在接受治疗的小鼠模型中,病态视网膜血管生成显著减少.

结论:

针对Pik3cd的AAV介导的CRISPR干扰是一种可行的策略,可以抑制PI3Kδ的表达.
这种方法在治疗眼睛病理性血管生成方面表现有前途.
开发的CRISPR/dCasX-KRAB系统适用于单个AAV矢量传递.

关键词:

这就是CRISPR/dCasX-KRAB.MT:编辑RNA/DNA的方法在PI3Kδδ 在Pik3cdd中使用Pik3cd.血管新生是因为血管新生.氧气诱导的视网膜病变 rAAV1 rAAV1 的意思

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