转导(生物物理学)
生物
转基因
中枢神经系统
腺相关病毒
遗传增强
基因传递
星形胶质细胞
全身给药
细胞生物学
脊髓
分子生物学
免疫学
载体(分子生物学)
基因
神经科学
重组DNA
遗传学
体内
生物化学
作者
Melvin Y. Rincón,Filip de Vin,Sandra Duqué,Shelly Fripont,Stéphanie A. Castaldo,Jessica Bouhuijzen-Wenger,Matthew G. Holt
出处
期刊:Gene Therapy
[Springer Nature]
日期:2018-03-09
卷期号:25 (2): 83-92
被引量:48
标识
DOI:10.1038/s41434-018-0005-z
摘要
Until recently, adeno-associated virus 9 (AAV9) was considered the AAV serotype most effective in crossing the blood-brain barrier (BBB) and transducing cells of the central nervous system (CNS), following systemic injection. However, a newly engineered capsid, AAV-PHP.B, is reported to cross the BBB at even higher efficiency. We investigated how much we could boost CNS transgene expression by using AAV-PHP.B carrying a self-complementary (sc) genome. To allow comparison, 6 weeks old C57BL/6 mice received intravenous injections of scAAV2/9-GFP or scAAV2/PHP.B-GFP at equivalent doses. Three weeks postinjection, transgene expression was assessed in brain and spinal cord. We consistently observed more widespread CNS transduction and higher levels of transgene expression when using the scAAV2/PHP.B-GFP vector. In particular, we observed an unprecedented level of astrocyte transduction in the cortex, when using a ubiquitous CBA promoter. In comparison, neuronal transduction was much lower than previously reported. However, strong neuronal expression (including spinal motor neurons) was observed when the human synapsin promoter was used. These findings constitute the first reported use of an AAV-PHP.B capsid, encapsulating a scAAV genome, for gene transfer in adult mice. Our results underscore the potential of this AAV construct as a platform for safer and more efficacious gene therapy vectors for the CNS.
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