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General Research Article

蛋白酶体抑制剂对AAV介导的视网膜双极细胞转导效率的影响。

卷 19, 期 6, 2019

页: [404 - 412] 页: 9

弟呕挨: 10.2174/1566523220666200211111326

价格: $65

摘要

背景：腺相关病毒（AAV）载体是将治疗性基因传递至视网膜的最有希望的载体。为了开发实用的基因传递工具，通常需要在特定细胞类型中实现高的AAV转导效率。在某些应用（例如光遗传疗法）中，需要在视网膜双极细胞中AAV介导的靶向表达，但是，内源性细胞特异性启动子驱动的转导效率通常较低。需要开发可以提高双极细胞中AAV转导效率的方法。 目的：该研究旨在检查蛋白酶体抑制剂对视网膜双极细胞中AAV介导的转导效率的影响。 方法：定量分析荧光报告蛋白的表达，以评估两种蛋白酶体抑制剂阿霉素和MG132对AAV介导的小鼠视网膜双极细胞转导效率的影响。 结果：我们的结果表明，阿霉素可以以剂量依赖性方式增加视网膜双极细胞中AAV的转导效率。我们还观察到了视网膜神经元中阿霉素介导的细胞毒性，但可通过右旋右雷佐生的联合应用减轻细胞毒性。与阿霉素（300μM）和右雷佐生共同应用三个月后，视网膜双极细胞中AAV的转导效率提高了33.8％，并且在视网膜的所有层中均未观察到细胞毒性。 结论：阿霉素可提高体内视网膜双极细胞的AAV转导效率。右雷佐生可以部分减轻阿霉素对视网膜神经元的潜在长期细胞毒性。阿霉素和右雷佐生的共同应用可作为潜在的佐剂方案，以提高视网膜双极细胞中AAV的转导效率。

关键词: 腺相关病毒，视网膜基因治疗，阿霉素，右雷佐生，视网膜，双极细胞。

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