Specific tools for targeting and expression in Muller glial cells

被引:40
|
作者
Pellissier, Lucie P. [1 ]
Hoek, Robert M. [1 ]
Vos, Rogier M. [1 ]
Aartsen, Wendy M. [1 ]
Klimczak, Ryan R. [2 ,3 ]
Hoyng, Stefan A. [4 ]
Flannery, John G. [2 ,3 ]
Wijnholds, Jan [1 ]
机构
[1] Netherlands Inst Neurosci, Dept Neuromed Genet, Amsterdam, Netherlands
[2] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA
[4] Netherlands Inst Neurosci, Dept Neuroregenerat, Amsterdam, Netherlands
关键词
RETINALDEHYDE-BINDING PROTEIN; CD44; GENE-EXPRESSION; IMMEDIATE-EARLY GENE; ADENOASSOCIATED VIRUS; TRANSDUCTION; PROMOTER; INTERLEUKIN-1-BETA; LOCALIZATION; RETINA; VECTOR;
D O I
10.1038/mtm.2014.9
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Despite their physiological roles, Muller glial cells are involved directly or indirectly in retinal disease pathogenesis and are an interesting target for therapeutic approaches for retinal diseases and regeneration such as CRB1 inherited retinal dystrophies. In this study, we characterized the efficiency of adeno-associated virus (AAV) capsid variants and different promoters to drive protein expression in Muller glial ces. ShH10Y and AAV9 were the most powerful capsids to infect mouse Muller glial cells. Retinaldehydebinding protein 1 (RLBP1) promoter was the most powerful promoter to transduce Muller glial cells. ShH10Y capsids and RLBP1 promoter targeted human Muller glial cells in vit. We also developed and tested smaller promoters to express the large CRB1 gene via AAV vectors. Minimal cytomegalovirus (CMV) promoter allowed expression of full-length CRB1 protein in Muller glial cells. In summary, ShH10Y and AAV9 capsids, and RLBP1 or minimal CMV promoters are of interest as specific tools to target and express in mouse or human Muller glial cells.
引用
收藏
页数:9
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