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.

基因疗法在解决与中枢和​​周围神经系统（CNS 和 PNS）相关的神经病理学方面提供了巨大的希望。然而，遗传获取仍然困难，这反映出迫切需要开发跨物种的有效和非侵入性基因传递载体。为此，我们在小鼠中进化出了腺相关病毒血清型 9 (AAV9) 衣壳，并在啮齿类动物（小鼠和大鼠）和非人类灵长类 (NHP) 物种（狨猴）中验证了两种衣壳：AAV-MaCPNS1 和 AAV-MaCPNS2和恒河猴）。静脉注射任一 AAV 均可有效转导啮齿动物中的三七总皂苷 (PNS) 以及非人类灵长类动物 (NHP) 中的三七总皂苷 (PNS) 和中枢神经系统 (CNS)。此外，我们在小鼠中使用 AAV-MaCPNS1 系统地传递以下信息：(1) 神经元传感器 jGCaMP8s 记录结状神经节中的钙信号动态，(2) 神经元致动器 DREADD 到背根神经节以介导疼痛。这最终证明了这两种系统性 AAV 在四个物种中的可翻译性及其通过小鼠概念验证研究的功能实用性。