Samaranch L, Blits B, San Sebastian W, Hadaczek P, Bringas J, Sudhakar V, Macayan M, Pivirotto P J, Petry H, Bankiewicz K S
Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Neurobiology, Research and Development, UniQure NV, Amsterdam 1105BA, The Netherlands.
Gene Ther. 2017 Apr;24(4):253-261. doi: 10.1038/gt.2017.14. Epub 2017 Mar 16.
The present study was designed to characterize transduction of non-human primate brain and spinal cord with AAV5 viral vector after parenchymal delivery. AAV5-CAG-GFP (1 × 10 vector genomes per milliliter (vg ml)) was bilaterally infused either into putamen, thalamus or with the combination left putamen and right thalamus. Robust expression of GFP was seen throughout infusion sites and also in other distal nuclei. Interestingly, thalamic infusion of AAV5 resulted in the transduction of the entire corticospinal axis, indicating transport of AAV5 over long distances. Regardless of site of injection, AAV5 transduced both neurons and astrocytes equally. Our data demonstrate that AAV5 is a very powerful vector for the central nervous system and has potential for treatment of a wide range of neurological pathologies with cortical, subcortical and/or spinal cord affection.
本研究旨在表征实质内递送后腺相关病毒5型（AAV5）病毒载体对非人类灵长类动物脑和脊髓的转导作用。将AAV5-CAG-GFP（每毫升1×10载体基因组（vg/ml））双侧注入壳核、丘脑，或同时注入左侧壳核和右侧丘脑。在整个注射部位以及其他远端核团均可见到绿色荧光蛋白（GFP）的强烈表达。有趣的是，向丘脑注射AAV5导致整个皮质脊髓轴的转导，表明AAV5可进行长距离运输。无论注射部位如何，AAV5对神经元和星形胶质细胞的转导作用相同。我们的数据表明，AAV5是一种用于中枢神经系统的非常强大的载体，具有治疗广泛的涉及皮质、皮质下和/或脊髓的神经病理学疾病的潜力。
