Bennett J, Maguire A M, Cideciyan A V, Schnell M, Glover E, Anand V, Aleman T S, Chirmule N, Gupta A R, Huang Y, Gao G P, Nyberg W C, Tazelaar J, Hughes J, Wilson J M, Jacobson S G
Department of Ophthalmology, F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9920-5. doi: 10.1073/pnas.96.17.9920.
Recombinant adeno-associated virus (rAAV) is a promising vector for therapy of retinal degenerative diseases. We evaluated the efficiency, cellular specificity, and safety of retinal cell transduction in nonhuman primates after subretinal delivery of an rAAV carrying a cDNA encoding green fluorescent protein (EGFP), rAAV. CMV.EGFP. The treatment results in efficient and stable EGFP expression lasting >1 year. Transgene expression in the neural retina is limited exclusively to rod photoreceptors. There is neither electroretinographic nor histologic evidence of photoreceptor toxicity. Despite significant serum antibody responses to the vector, subretinal readministration results in additional transduction events. The findings further characterize the retinal cell tropism of rAAV. They also support the development of studies aimed ultimately at treating inherited retinal degeneration by using rAAV-mediated gene therapy.
重组腺相关病毒（rAAV）是治疗视网膜退行性疾病的一种很有前景的载体。我们评估了在非人灵长类动物视网膜下注射携带编码绿色荧光蛋白（EGFP）的cDNA的rAAV（rAAV.CMV.EGFP）后视网膜细胞转导的效率、细胞特异性和安全性。该治疗导致高效且稳定的EGFP表达持续超过1年。转基因在神经视网膜中的表达仅局限于视杆光感受器。没有视网膜电图或组织学证据表明光感受器有毒性。尽管对载体有显著的血清抗体反应，但视网膜下再次给药会导致额外的转导事件。这些发现进一步明确了rAAV的视网膜细胞嗜性。它们还支持了最终旨在通过使用rAAV介导的基因疗法治疗遗传性视网膜变性的研究的开展。
