- 作者: Henrique Cheng; Stephanie H. Wolfe; Valery Valencia; Keping Qian; Leping Shen; M. Ian Phillips; Lung-Ji Chang; Y. Clare Zhang
- 作者服務機構: 1 Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA; ; 2 Childrens Research Institute, Department of Pediatrics, University of South Florida, 140 7th Ave S, CRI 2006, St. Petersburg, FA, 33701, USA; ; 3 Keck Graduate Institute, Claremont, CA, USA; ; 4 Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, FL, USA; 5 Department of Pathology, University of Florida, Gainesville, FL, USA
- 中文摘要: --
- 英文摘要: 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.
- 中文關鍵字: --
- 英文關鍵字: adeno-associated virus, lentivirus, pancreas, β-cells, gene therapy