Department of Pathology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Gene Ther. 2011 Jul;18(7):682-91. doi: 10.1038/gt.2011.13. Epub 2011 Mar 3.
Gene transfer to central nervous system (CNS) has been approached using various vectors. Recombinant SV40-derived vectors (rSV40s) transduce human neurons and microglia effectively in vitro and in rodent brains in vivo, so we tested rSV40s gene transfer to rhesus monkey CNS in vivo, to characterize the distribution, duration and safety of such gene delivery. We used rSV40s carrying HIV-1 RevM10 with a carboxyl-terminal AU1 epitope tag as a marker, and others with the antioxidant enzymes, Cu/Zn superoxide dismutase and glutathione peroxidase. Vectors were injected stereotaxically into the caudate nucleus. Transgene expression was studied at 1 and 6 months by immunostaining serial brain sections. After intraparenchymal administration, numerous transgene-expressing cells were seen, with a longitudinal extent of 20 mm. In neurons and, more rarely, microglial cells, transgene expression remained strong throughout the 6-month study period. Astrocytes and oligodendroglia were not transduced. No evidence of inflammation or tissue damage was observed. SV40-derived vectors may thus be useful for long-term gene expression in the monkey brain and, potentially, in the human brain.
基因转移到中枢神经系统（CNS）已采用了各种载体。重组 SV40 衍生的载体（rSV40）有效地转导体外培养的人类神经元和小胶质细胞，并在体内的啮齿动物脑中转导，因此我们测试了 rSV40 对恒河猴 CNS 的体内基因转移，以描述这种基因传递的分布、持续时间和安全性。我们使用 rSV40 携带 HIV-1 RevM10 的羧基末端 AU1 表位标签作为标记，以及其他抗氧化酶，铜/锌超氧化物歧化酶和谷胱甘肽过氧化物酶。载体通过立体定向注射到尾状核。通过免疫染色连续脑切片，在 1 和 6 个月时研究转基因表达。在脑实质内给药后，可见大量表达转基因的细胞，纵向延伸 20mm。在神经元中，更罕见的是小胶质细胞中，转基因表达在整个 6 个月的研究期间保持强烈。星形胶质细胞和少突胶质细胞没有被转导。未观察到炎症或组织损伤的证据。因此，SV40 衍生的载体可能对猴脑和可能的人脑中的长期基因表达有用。
