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Celastrol enhances AAV1-mediated gene expression in mice adipose tissues

Gene Therapy volume 18, pages 128–134 (2011)Cite this article

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Abstract

The transduction of adeno-associated virus (AAV) in adipose tissues was not well characterized and appeared to be insufficient as compared with other targeted tissues in gene therapy. We have found that celastrol, a chemical from a traditional Chinese herb known to inhibit the proteasome activity, was able to enhance the transgene expression mediated by AAV1 in 3T3-L1 preadipocytes both before and after induced differentiation. A synergism of celastrol and nonionic surfactant pluronic F68 cotreatment on AAV1 transduction was observed in the experiments with rat primary preadipocyte cultures and in adipose tissues in vivo. By fluorescent microscopy using Alexa Fluor 647-labeled AAV and quantitative PCR assays, we found that celastrol treatments increased the nuclear distribution of AAV genomic DNAs, but not the total amount of viral cellular uptake in preadipocytes, which was different from the effect of pluronic F68 treatment to significantly promote the AAV internalization. Our data suggested that bioactive monomeric compounds extracted from herbal medicines might be used to facilitate AAV-mediated gene transfer applications.

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Acknowledgements

This study was supported by the Chinese Natural Science Foundation project 30771062, 30970161, and by the Beijing Municipal Fund for Advanced Higher Education 2008. We thank professor Wei-Ming Duan from the Department of Human Anatomy and Embryology at Capital Medical University for his comments for the revision of this paper.

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  1. Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China

    F-L Zhang, S-Q Jia, S-P Zheng & W Ding

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  1. F-L Zhang
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Correspondence to W Ding.

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Zhang, FL., Jia, SQ., Zheng, SP. et al. Celastrol enhances AAV1-mediated gene expression in mice adipose tissues. Gene Ther 18, 128–134 (2011). https://doi.org/10.1038/gt.2010.120

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