Department of Neuromedical Genetics, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences , Amsterdam, The Netherlands.
Department of Molecular and Cellular Biology and The Helen Wills Neuroscience Institute, University of California , Berkeley, California, USA.
Mol Ther Methods Clin Dev. 2014 Mar 19;1:14009. doi: 10.1038/mtm.2014.9. eCollection 2014.
Despite their physiological roles, Müller 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 Müller glial cells. ShH10Y and AAV9 were the most powerful capsids to infect mouse Müller glial cells. Retinaldehyde-binding protein 1 (RLBP1) promoter was the most powerful promoter to transduce Müller glial cells. ShH10Y capsids and RLBP1 promoter targeted human Müller glial cells in vitro. 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 Müller 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 Müller glial cells.
尽管 Muller 胶质细胞具有生理作用，但它们直接或间接地参与了视网膜疾病的发病机制，并且是治疗视网膜疾病和再生的有前途的靶点，例如 CRB1 遗传性视网膜营养不良。在这项研究中，我们描述了腺相关病毒（AAV）衣壳变体和不同启动子在 Muller 胶质细胞中驱动蛋白表达的效率。ShH10Y 和 AAV9 是感染小鼠 Muller 胶质细胞的最有效衣壳。视黄醛结合蛋白 1（RLBP1）启动子是转导 Muller 胶质细胞的最有效启动子。ShH10Y 衣壳和 RLBP1 启动子在体外靶向人 Muller 胶质细胞。我们还开发并测试了较小的启动子，通过 AAV 载体表达大型 CRB1 基因。最小的巨细胞病毒（CMV）启动子允许 Muller 胶质细胞中全长 CRB1 蛋白的表达。总之，ShH10Y 和 AAV9 衣壳以及 RLBP1 或最小 CMV 启动子是作为靶向和表达小鼠或人 Muller 胶质细胞的特定工具的候选物。
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