Your browser doesn't support javascript.
loading
Targeting adipose tissue via systemic gene therapy.
O'Neill, S M; Hinkle, C; Chen, S-J; Sandhu, A; Hovhannisyan, R; Stephan, S; Lagor, W R; Ahima, R S; Johnston, J C; Reilly, M P.
Afiliación
  • O'Neill SM; Cardiovascular Institute, Translational Research Center, University of Pennsylvania, Philadelphia, PA, USA.
  • Hinkle C; Cardiovascular Institute, Translational Research Center, University of Pennsylvania, Philadelphia, PA, USA.
  • Chen SJ; Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Sandhu A; Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Hovhannisyan R; Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Stephan S; Cardiovascular Institute, Translational Research Center, University of Pennsylvania, Philadelphia, PA, USA.
  • Lagor WR; Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Ahima RS; 1] Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA [2] The Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Johnston JC; Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Reilly MP; Cardiovascular Institute, Translational Research Center, University of Pennsylvania, Philadelphia, PA, USA.
Gene Ther ; 21(7): 653-61, 2014 Jul.
Article en En | MEDLINE | ID: mdl-24830434
Adipose tissue has a critical role in energy and metabolic homeostasis, but it is challenging to adapt techniques to modulate adipose function in vivo. Here we develop an in vivo, systemic method of gene transfer specifically targeting adipose tissue using adeno-associated virus (AAV) vectors. We constructed AAV vectors containing cytomegalovirus promoter-regulated reporter genes, intravenously injected adult mice with vectors using multiple AAV serotypes, and determined that AAV2/8 best targeted adipose tissue. Altering vectors to contain adiponectin promoter/enhancer elements and liver-specific microRNA-122 target sites restricted reporter gene expression to adipose tissue. As proof of efficacy, the leptin gene was incorporated into the adipose-targeted expression vector, package into AAV2/8 and administered intravenously to 9- to 10-week-old ob/ob mice. Phenotypic changes were measured over an 8-week period. Leptin mRNA and protein were expressed in adipose and leptin protein was secreted into plasma. Mice responded with reversal of weight gain, decreased hyperinsulinemia and improved glucose tolerance. AAV2/8-mediated systemic delivery of an adipose-targeted expression vector can replace a gene lacking in adipose tissue and correct a mouse model of human disease, demonstrating experimental application and therapeutic potential in disorders of adipose.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Tejido Adiposo / Dependovirus / Marcación de Gen / Vectores Genéticos Límite: Animals / Humans / Male Idioma: En Revista: Gene Ther Asunto de la revista: GENETICA MEDICA / TERAPEUTICA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Tejido Adiposo / Dependovirus / Marcación de Gen / Vectores Genéticos Límite: Animals / Humans / Male Idioma: En Revista: Gene Ther Asunto de la revista: GENETICA MEDICA / TERAPEUTICA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido