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ORIGINAL RESEARCH article
Front. Med.
Sec. Gene and Cell Therapy
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1554449
This article is part of the Research Topic Recent Trends in Viral Mediated Gene Therapy in Human Diseases View all articles
High Homology Revisited: Distinct Infectivity and Neutralization Antibody Responses in Closely Related AAV Go.1 and AAV5
Provisionally accepted- 1 First People's Hospital of Foshan, Foshan, China
- 2 Institute of Neuroscience and Brain Diseases, Xiangyang Central Hospital, Xiangyang, China
- 3 Department of Precision Measurement Physics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan, Hebei Province, China
- 4 School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
- 5 Department of Anesthesiology, First People's Hospital of Foshan, Foshan, Guangdong Province, China
Goat-derived adeno-associated virus (AAV) vectors, such as AAV Go.1, offer a novel approach for gene therapy due to their unique origin and potential advantages. In this study, we reported the use of goat-derived rAAV Go.1 for enhanced gene delivery and immune evasion. To produce rAAV Go.1, we replaced the goat AAV rep with the standard AAV2-rep gene, resulting in a significantly higher packaging efficiency than the original goat AAV. In comparison to the AAV5 serotype (a goat AAV analogue with 95% genome similarity), rAAV Go.1 exhibited substantially higher transduction efficiency both in vitro and in vivo. Moreover, in comparison to AAV5, AAV Go.1 demonstrated a 4fold increase in resistance to neutralization by sera from rAAV5-immunized mice. We observed that neutralizing antibodies with a high titer had a more inhibitory effect on the cell transduction of rAAV5 in a study involving 20 healthy volunteers. To further enhance transduction efficiency, we introduced mutations in the VP1 unique (VP1u) region or VP1/2 common region. Notably, mutations K32R, K91R and K122R in the VP1u region significantly increased viral production, while mutations K137R (VP1u) enhanced cell transduction in vitro and in vivo. The rAAV Go.1 presents a novel and promising gene therapy vector with improved transduction efficiency and immunogenicity.
Keywords: Gene Therapy, rAAV Go.1, Cell transfection, neutralizing antibody, Packaging efficiency
Received: 02 Jan 2025; Accepted: 27 Feb 2025.
Copyright: © 2025 Mei, Ma, Wu, Gao, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jie Wang, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Shanghai Municipality, China
Hanbing Wang, Department of Anesthesiology, First People's Hospital of Foshan, Foshan, 528300, Guangdong Province, China
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