Ali R R, Reichel M B, Thrasher A J, Levinsky R J, Kinnon C, Kanuga N, Hunt D M, Bhattacharya S S
Department of Molecular Genetics, University College London, UK.
Hum Mol Genet. 1996 May;5(5):591-4. doi: 10.1093/hmg/5.5.591.
Gene transfer to photoreceptor cells may provide a means for arresting the retinal degeneration that is characteristic of many inherited causes of blindness, including retinitis pigmentosa (RP). However, transduction of photoreceptors has to date been inefficient, and further limited by toxicity and immune responses directed against vector-specific proteins. An alternative vector system based on adeno-associated virus (AAV) may obviate these problems, and may be useful for transduction of neuronal cells. In this study we have demonstrated successful transduction of all layers of the neuroretina as well as the retinal pigment epithelium (RPE) following subretinal injection of recombinant AAV particles encoding lac Z. Furthermore, the efficiency of transduction of photoreceptors is significantly higher than that achieved with an equivalent adenoviral vector. This is the first report showing that AAV is capable of transducing photoreceptor cells and supports the use of this vector system for gene therapy of retinal diseases such as RP.
将基因转移至光感受器细胞可能为阻止视网膜变性提供一种方法，视网膜变性是许多遗传性致盲病因（包括色素性视网膜炎，即RP）的特征。然而，迄今为止，光感受器的转导效率低下，并且还受到针对载体特异性蛋白的毒性和免疫反应的进一步限制。基于腺相关病毒（AAV）的替代载体系统可能会避免这些问题，并且可能对神经元细胞的转导有用。在本研究中，我们已经证明，在视网膜下注射编码lac Z的重组AAV颗粒后，神经视网膜的所有层以及视网膜色素上皮（RPE）均成功实现了转导。此外，光感受器的转导效率明显高于使用等效腺病毒载体所达到的效率。这是第一份表明AAV能够转导光感受器细胞的报告，并支持将该载体系统用于诸如RP等视网膜疾病的基因治疗。
