Doxorubicin accelerates and enhances AAV-based transgene expression in the cat and rat brain
Gong Hongliang1,2; Lu Yiliang1; Qian Liling1; I.Andolina1; Liu Rui3; Zhang Shenghai3; Zilong Qiu1; Wu Jihong3; Wang Wei1
Conference Name2017年第二届曲阜视觉科学会议
Correspondent ;
Conference Date2017.7.2
Conference Place曲阜

PURPOSE: Recombinant adeno-associated viruses (AAV) are widely used vectors for gene transfer into the central nervous system (CNS).However, Low transduction efficiency andthe delay in transgene expression have hampered it from wide application in such as early embryonic development and the brain of higher mammals for both basic and clinic researches. This study is designed to establish a new means to improve both the efficiency and timing of AAV transduction in transgene expression.  
METHODS: By co-administration of doxorubicin with AAV8 vector into the cortex of cat, we firstly evaluated the effect of doxorubicin on enhancing vector transfection and transgene expression at different time points after infection. Then, we characterized the dose dependence of doxorubicin on AAV-mediated gene expression by varying the concentration of doxorubicin. The toxicity of doxorubicin was also examined by cell apoptosis assay.   
RESULTS:Local administration of 10 μg/mL doxorubicin remarkably facilitated AAV8-based gene transfer to neurons, increasing both cell numbers and expression level of GFP. The doxorubicin accelerated GFP expression is observed to appear as earlier as the third day after infection, and increased GFP intensity is persistent through the following multiple weeks in time. Doxorubicin was found to increase the neural expression of GFP at doses between 0.1 ~ 10 μg/mL with little toxicity, but induced neuron loss at a dose higher than 30 μg/mL.
CONCLUSIONS:Co-infusion of doxorubicin accelerates AAV-based transgene expression in the cortex of higher mammals. This improved efficiency and timing of AAV transduction might have great potentials in the application for early embryonic development and other neurophysiological research for CNS diseases in higher mammals.       

KeywordAAV doxorubicin gene transfer cat visual cortex
Document Type会议论文
Corresponding AuthorWu Jihong; Wang Wei
Affiliation1.Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences
2.University of Chinese Academy of Sciences
3.Department of Ophthalmology, EYE and ENT Hospital of Fudan University, Key Laboratory of Myopia of State Health Ministry and Key Laboratory of Visual Impairment and Restoration of Shanghai
Recommended Citation
GB/T 7714
Gong Hongliang,Lu Yiliang,Qian Liling,et al. Doxorubicin accelerates and enhances AAV-based transgene expression in the cat and rat brain[C],2017.
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