title: Efficient and persistent transduction of exocrine and endocrine pancreas by adeno-associated virus type 8.
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.
authors: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
authors: Henrique
authors: H
authors: Cheng
authors: Stephanie H
authors: SH
authors: Wolfe
authors: Valery
authors: V
authors: Valencia
authors: Keping
authors: K
authors: Qian
authors: Leping
authors: L
authors: Shen
authors: M Ian
authors: MI
authors: Phillips
authors: Lung-Ji
authors: LJ
authors: Chang
authors: Y Clare
authors: YC
authors: Zhang
mesh_terms: D000818:Animals; D001786:Blood Glucose; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D046790:Pancreas, Exocrine / Q000166:cytology; D014161:Transduction, Genetic
chemical_list: D001786:Blood Glucose; D049452:Green Fluorescent Proteins