Celastrol enhances AAV1-mediated gene expression in mice adipose tissues

• Published in: Gene therapy Vol. 18; no. 2; pp. 128 - 134
• Main Authors: Zhang, F-L, Jia, S-Q, Zheng, S-P, Ding, W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2011; Nature Publishing Group
• Subjects: 3T3 Cells; 631/1647/2300; 631/326/596/2561; 631/61/201; 631/92/349; Adeno-associated virus; Adenoviruses; Adipose Tissue; Adipose tissues; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antioxidants; Applied cell therapy and gene therapy; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cell Biology; Cell culture; Dependovirus - genetics; Dependoviruses; enabling-technologies; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Regulation; Gene Targeting; Gene Therapy; Gene Transfer Techniques; Genetic aspects; Genetic Vectors; Health. Pharmaceutical industry; Herbal medicine; Human Genetics; Industrial applications and implications. Economical aspects; Internalization; Medical sciences; Mice; Nanotechnology; Physiological aspects; Poloxamer - pharmacology; Preadipocytes; Properties; Protease inhibitors; Proteasomes; Rodents; Signal transduction; Transduction, Genetic - methods; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Triterpenes - pharmacology; China; adeno-associated virus; proteasome inhibitor; adipocytes; herbal medicine; Adipocyte; Multicatalytic endopeptidase complex; Adipose tissue; Enzyme; Rodentia; Dependovirus; Gene expression; Virus; Medicine; Peptidases; Vertebrata; Mammalia; Mouse; Parvoviridae; Hydrolases; Inhibitor; Gene therapy; Parvovirinae
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/gt.2010.120

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.