腺相关病毒基因转移至小鼠视网膜。

Adeno-associated virus gene transfer to mouse retina.

作者信息

Ali R R, Reichel M B, De Alwis M, Kanuga N, Kinnon C, Levinsky R J, Hunt D M, Bhattacharya S S, Thrasher A J

机构信息

Department of Molecular Genetics, Institute of Ophthalmology, University College London, UK.

出版信息

Hum Gene Ther. 1998 Jan 1;9(1):81-6. doi: 10.1089/hum.1998.9.1-81.

DOI:10.1089/hum.1998.9.1-81

PMID:9458245

Abstract

Ocular gene transfer may provide a means for arresting the retinal degeneration characteristic of many inherited causes of blindness, including retinitis pigmentosa (RP). Previously, we have shown in immunodeficient animals that recombinant adeno-associated virus (rAAV) mediates transduction of photoreceptors as well as the retinal pigment epithelium (RPE) following subretinal injection. In this study we extend these observations and show that highly purified recombinant AAV vectors encoding the reporter gene LacZ transduce photoreceptors in an immunocompetent mouse strain following subretinal injection and efficiently transduce ganglion cells after intravitreal injection. Levels of transduction increase over time. Sublethal gamma-irradiation is shown to facilitate this process.

摘要

眼部基因转移可能为阻止许多遗传性致盲原因所特有的视网膜变性提供一种手段，包括色素性视网膜炎（RP）。此前，我们已在免疫缺陷动物中表明，重组腺相关病毒（rAAV）在视网膜下注射后介导光感受器以及视网膜色素上皮（RPE）的转导。在本研究中，我们扩展了这些观察结果，并表明编码报告基因LacZ的高度纯化的重组AAV载体在视网膜下注射后可转导具有免疫活性的小鼠品系中的光感受器，并且在玻璃体内注射后可有效转导神经节细胞。转导水平随时间增加。亚致死剂量的γ射线照射显示有助于这一过程。