Develop an efficient and specific AAV-based labeling system for Muller glia in mice

文献类型： 外文期刊

第一作者： Gao, Yanxia

作者： Gao, Yanxia;Fang, Kailun;Yan, Zixiang;Geng, Guannan;Wu, Weiwei;Wang, Qifang;Cai, Minqing;Yang, Hui;Zhang, Haiwei;Zuo, Erwei;Xu, Ding;Zhang, Heng;Zhong, Na

作者机构：

期刊名称：SCIENTIFIC REPORTS （ 影响因子：4.6； 五年影响因子：4.9 ）

ISSN： 2045-2322

年卷期： 2022 年 12 卷 1 期

页码：

收录情况： SCI

摘要： Reprogramming Muller glia (MG) into functional cells is considered a promising therapeutic strategy to treat ocular diseases and vision loss. However, current AAV-based system for MG-tracing was reported to have high leakage in recent studies. Here, we focused on reducing the leakage of AAV-based labeling systems and found that different AAV serotypes showed a range of efficiency and specificity in labeling MG, leading us to optimize a human GFAP-Cre reporter system packaged in the AAV9 serotype with the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) removed. The leakage ratio of the AAV9-hGFAP-Cre-Delta WPRE decreased by an approximate 40-fold compared with the AAV9-hGFAP-Cre-WPRE labeling system. In addition, we validated the specificity of the AAV-Delta WPRE system for tracing MG reprogramming under Ptbp1-suppression and observed strict non-MG-conversion, similar to previous studies using genetic lineage tracking mouse models. Thus, the AAV9-hGFAP-Cre-Delta WPRE system showed high efficiency and specificity for MG labeling, providing a promising tool for tracing cell fate in vivo.

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