title: Genetic Manipulation of Brown Fat Via Oral Administration of an Engineered Recombinant Adeno-associated Viral Serotype Vector.
abstract: Recombinant adeno-associated virus (rAAV) vectors are attractive vehicles for gene therapy. Gene delivery to the adipose tissue using naturally occurring AAV serotypes is less successful compared to liver and muscle. Here, we demonstrate that oral administration of an engineered serotype Rec2 led to preferential transduction of brown fat with absence of transduction in the gastrointestinal track. Among the six natural and engineered serotypes being compared, Rec2 was the most efficient serotype achieving high level transduction at a dose 1~2 orders lower than reported doses for systemic administration. Overexpressing vascular endothelial growth factor (VEGF) in brown fat via oral administration of Rec2-VEGF vector increased the brown fat mass and enhanced thermogenesis. In contrast, knockdown VEGF in brown fat of VEGF (loxP) mice via Rec2-Cre vector hampered cold response and decreased brown fat mass. Oral administration of Rec2 vector provides a novel tool to genetically manipulate brown fat for research and therapeutic applications.
authors: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USA; The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
authors: Wei
authors: W
authors: Huang
authors: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USA; The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
authors: Travis
authors: T
authors: McMurphy
authors: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USA; The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
authors: Xianglan
authors: X
authors: Liu
authors: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USA; The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
authors: Chuansong
authors: C
authors: Wang
authors: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, USA; The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA. Electronic address: lei.cao@osumc.edu.
authors: Lei
authors: L
authors: Cao
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000229:Dependovirus / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage*; D051379:Mice; D009928:Organ Specificity; D022722:Thermogenesis / Q000187:drug effects; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A