A Comprehensive Study of AAV Tropism in the Marmoset Brain
Kailun Fang1,2 · Hailin Liu1 · Yuting Yao1,3 · Zhen Xu1 · Xinyu Liu1 · Canbin Feng1 · Yuanhua Liu1,2,4 · Tong Li5 · Guannan Geng1,2,6 · Ruoxi Wu7 · Junhui Xia7 · Fan Yang1,2 · Linyu Shi7 · Hui Yang1,2,5,7 · Neng Gong1,2,3
1 Institute of Neuroscience, Key Laboratory of Brain Cognition and Brain‑inspired Intelligence Technology, Center for Excellence in Brain Science and Intelligence Technology, International Center for Primate Brain Research, Chinese Academy of Sciences, Shanghai 200031, China
2 Shanghai Center for Brain Science and Brain-Inspired Technology, Shanghai 201602, China
3 University of Chinese Academy of Sciences, Beijing 101408, China
4 State Key Laboratory of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
5 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
6 ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai 200031, China
7 HuidaGene Therapeutics Co., Ltd., Shanghai 200131, China
Abstract
The common marmoset has emerged as an increasingly valuable non-human primate model in neuroscience and biomedical research. Recombinant adeno-associated viruses (AAVs) are powerful tools for gene delivery and gene therapy. However, a systematic comparison of different AAV capsids and delivery routes remains lacking in marmosets. In this study, we constructed a barcoded AAV library comprising 21 capsid variants and administered it to marmosets via intravenous, intraventricular, and intrastriatal injections. To evaluate the AAV tropism, we quantified vector DNA, viral RNA abundance, and tdTomato signals in the marmoset brain and other tissues. Intravenous administration led to limited brain transduction, while intraventricular and intrastriatal administrations demonstrated high transduction efficiency in the marmoset brain. Notably, some AAV capsids exhibited distinct transduction patterns in the marmoset brain. These results offer valuable guidance for optimizing AAV-based gene delivery strategies in marmoset models and support their utility in both basic neuroscience research and potential therapeutic applications.
Keywords
AAV tropism; Marmoset; Central nervous system; Intraventricular injection; Intrastriatal injection; Intravenous injection
