In vivo gene transfer to pancreatic beta cells by systemic delivery of adenoviral vectors.
Type 1 diabetes results from autoimmune destruction of pancreatic beta cells. This process might be reversed by genetically engineering the endocrine pancreas in vivo to express factors that induce beta cell replication and neogenesis and counteract the immune response. However, the pancreas is difficult to manipulate and pancreatitis is a serious concern, which has made effective gene transfer to this organ elusive. Thus, new approaches for gene delivery to the pancreas in vivo are required. Here we show that pancreatic beta cells were efficiently transduced to express beta-galactosidase after systemic injection of adenovirus into mice with clamped hepatic circulation. Seven days after vector administration about 70% of pancreatic islets showed beta-galactosidase expression, with an average of about 20% of the cells within positive islets being transduced. In addition, scattered acinar cells expressing beta-galactosidase were also observed. Thus, this approach may be used to transfer genes of interest to mouse islets and beta cells, both for the study of islet biology and gene therapy of diabetes and other pancreatic disorders.
Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
Eduard
E
Ayuso
Miguel
M
Chillón
Judith
J
Agudo
Virginia
V
Haurigot
Assumpció
A
Bosch
Ana
A
Carretero
Pedro J
PJ
Otaegui
Fàtima
F
Bosch
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods; D001616:beta-Galactosidase / Q000378:metabolism*
D001616:beta-Galactosidase