Fang Kailun, Yang Xiali, Liu Yuanhua, Xia Junhui, Wu Ruoxi, Yang Fan, Feng Canbin, Liu Xinyu, Shi Linyu, Geng Guannan, Yang Hui
Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Center for Brain Science and Brain-Inspired Intelligence, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Huidagene Therapeutics Inc., Shanghai 200131, China.
Mol Ther Methods Clin Dev. 2025 Feb 13;33(1):101434. doi: 10.1016/j.omtm.2025.101434. eCollection 2025 Mar 13.
Recombinant adeno-associated viruses (AAVs) have been widely used for gene delivery and gene therapy. However, certain AAV serotypes exhibited distinct transduction patterns among different mouse strains or between mice and non-human primates (NHPs). These variations prompted us to investigate the AAV tropism of 21 capsid variants using barcoded AAV libraries among different tissues in C57BL/6 and BALB/c mice, as well as in crab-eating macaques. Our study unveiled that AAV tropisms varied significantly among different mouse strains and species, particularly in capsid variants such as AAV4, AAV9, PHP.B, and CAP-B10. Notably, AAV4 exhibited liver-detargeting properties in both mice and NHPs, and was remarkably efficient in transducing the lung, glomerulus, and pancreatic islet. These findings furnish crucial insights into the variations of AAV tropism among different mouse strains and species and facilitate the selection of appropriate AAV capsids for target tissues among different mouse strains and in NHPs.
重组腺相关病毒（AAV）已被广泛用于基因递送和基因治疗。然而，某些AAV血清型在不同小鼠品系之间或小鼠与非人类灵长类动物（NHP）之间表现出不同的转导模式。这些差异促使我们使用条形码化的AAV文库，在C57BL/6和BALB/c小鼠以及食蟹猕猴的不同组织中研究21种衣壳变体的AAV嗜性。我们的研究表明，AAV嗜性在不同小鼠品系和物种之间存在显著差异，特别是在AAV4、AAV9、PHP.B和CAP-B10等衣壳变体中。值得注意的是，AAV4在小鼠和NHP中均表现出肝脏脱靶特性，并且在转导肺、肾小球和胰岛方面非常有效。这些发现为不同小鼠品系和物种之间AAV嗜性的差异提供了关键见解，并有助于在不同小鼠品系和NHP中为靶组织选择合适的AAV衣壳。
