神经科学
腺相关病毒
生物
中枢神经系统
遗传增强
啮齿动物
灵长类动物
基因传递
衣壳
病毒载体
基因
病毒学
载体(分子生物学)
病毒
遗传学
重组DNA
生态学
作者
Xinhong Chen,Sripriya Ravindra Kumar,Cameron Adams,Daping Yang,Tongtong Wang,Damien Wolfe,Cynthia Mary Arokiaraj,Victoria K. Ngo,Lillian Gonçalves Campos,Jessica A. Griffiths,Takako Ichiki,Sarkis K. Mazmanian,Peregrine B. Osborne,Janet R. Keast,Cory T. Miller,Andrew J. Fox,Isaac M. Chiu,Viviana Gradinaru
出处
期刊:Neuron
[Elsevier]
日期:2022-07-01
卷期号:110 (14): 2242-2257.e6
被引量:37
标识
DOI:10.1016/j.neuron.2022.05.003
摘要
Summary
Gene therapy offers great promise in addressing neuropathologies associated with the central and peripheral nervous systems (CNS and PNS). However, genetic access remains difficult, reflecting the critical need for the development of effective and non-invasive gene delivery vectors across species. To that end, we evolved adeno-associated virus serotype 9 (AAV9) capsid in mice and validated two capsids, AAV-MaCPNS1 and AAV-MaCPNS2, across rodent species (mice and rats) and non-human primate (NHP) species (marmosets and rhesus macaques). Intravenous administration of either AAV efficiently transduced the PNS in rodents and both the PNS and CNS in NHPs. Furthermore, we used AAV-MaCPNS1 in mice to systemically deliver the following: (1) the neuronal sensor jGCaMP8s to record calcium signal dynamics in nodose ganglia and (2) the neuronal actuator DREADD to dorsal root ganglia to mediate pain. This conclusively demonstrates the translatability of these two systemic AAVs across four species and their functional utility through proof-of-concept studies in mice.
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