Transduction catalysis: Doxorubicin amplifies rAAV-mediated gene expression in the cortex of higher-order vertebrates
Hongliang Gong,
Nini Yuan,
Zhiming Shen,
Cheng Tang,
Stewart Shipp,
Liling Qian,
Yiliang Lu,
Ian Max Andolina,
Shenghai Zhang,
Jihong Wu,
Hui Yang,
Wei Wang
Affiliations
Hongliang Gong
Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China
Nini Yuan
Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China
Zhiming Shen
Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China
Cheng Tang
Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China
Stewart Shipp
Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China
Liling Qian
Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China
Yiliang Lu
Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China
Ian Max Andolina
Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China
Shenghai Zhang
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China
Jihong Wu
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China
Hui Yang
Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; Shanghai Center for Brain and Brain-Inspired Intelligence Technology, Shanghai 200031, China
Wei Wang
Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; Shanghai Center for Brain and Brain-Inspired Intelligence Technology, Shanghai 200031, China; Corresponding author
Summary: Rapid and efficient gene transduction via recombinant adeno-associated viruses (rAAVs) is highly desirable across many basic and clinical research domains. Here, we report that vector co-infusion with doxorubicin, a clinical anti-cancer drug, markedly enhanced rAAV-mediated transgene expression in the cerebral cortex across mammalian species (cat, mouse, and macaque), acting throughout the time period examined and detectable at just three days after transfection. This enhancement showed serotype generality, being common to all rAAV serotypes tested (2, 8, 9, and PHP.eB) and was observed both locally and at remote locations consistent with doxorubicin undergoing retrograde axonal transport. All these effects were observed at doses matching human blood plasma levels in clinical therapy and lacked detectable cytotoxicity as assessed by cell morphology, activity, apoptosis, and behavioral testing. Altogether, this study identifies an effective means to improve the capability and scope of in vivo rAAV applications, amplifying cell transduction at doxorubicin concentrations paralleling medical practice.
