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Efficient and persistent transduction of exocrine and endocrine pancreas by adeno-associated virus type 8

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Journal of Biomedical Science

Abstract

Efficient delivery of therapeutic proteins into the pancreas represents a major obstacle to gene therapy of pancreatic disorders. The current study compared the efficiency of recombinant lentivirus and adeno-associated virus (AAV) serotypes 1, 2, 5, 8 vectors delivered by intrapancreatic injection for gene transfer in vivo. Our results indicate that lentivirus and AAV 1, 2, 8 are capable of transducing pancreas with the order of efficiency AAV8 >>AAV1 > AAV2 ≥ lentivirus, whereas AAV5 was ineffective. AAV8 resulted in an efficient, persistent (150 days) and dose-dependent transduction in exocrine acinar cells and endocrine islet cells. Pancreatic ducts and blood vessels were also transduced. Extrapancreatic transduction was restricted to liver. Leukocyte infiltration was not observed in pancreas and blood glucose levels were not altered. Thus, AAV8 represents a safe and effective vehicle for therapeutic gene transfer to pancreas in vivo.

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Acknowledgements

This work is in part supported by the American Heart Association grant ( 0435243N, National Institute of Health grant R01 HL067248, and a private donation from John Horst, Tampa, Florida.

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Authors and Affiliations

  1. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA

    Henrique Cheng

  2. Children’s Research Institute, Department of Pediatrics, University of South Florida, 140 7th Ave S, CRI 2006, St. Petersburg, FA, 33701, USA

    Stephanie H. Wolfe, Valery Valencia & Y. Clare Zhang

  3. Keck Graduate Institute, Claremont, CA, USA

    Keping Qian, Leping Shen & M. Ian Phillips

  4. Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, FL, USA

    Lung-Ji Chang

  5. Department of Pathology, University of Florida, Gainesville, FL, USA

    Keping Qian, Leping Shen & M. Ian Phillips

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  1. Henrique Cheng
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  2. Stephanie H. Wolfe
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  3. Valery Valencia
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Correspondence to Y. Clare Zhang.

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Cheng, H., Wolfe, S.H., Valencia, V. et al. Efficient and persistent transduction of exocrine and endocrine pancreas by adeno-associated virus type 8. J Biomed Sci 14, 585–594 (2007). https://doi.org/10.1007/s11373-007-9159-1

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  • DOI: https://doi.org/10.1007/s11373-007-9159-1

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