Adipose tissue insulin receptor knockdown via a new primate-derived hybrid recombinant AAV serotype.
Adipose tissue plays an essential role in metabolic homeostasis, and holds promise as an alternative depot organ in gene therapy. However, efficient methods of gene transfer into adipose tissuein vivohave yet to be established. Here we assessed the transduction efficiency to fat depots by a family of novel engineered hybrid capsid serotypes (Rec1~4) recombinant AAV vectors in comparison with natural serotypes AAV1, AAV8, and AAV9. Rec2 serotype led to widespread transduction in both brown fat and white fat with the highest efficiency among the seven serotypes tested. As a proof-of-efficacy, Rec2 serotype was used to deliver Cre recombinase to adipose tissues of insulin receptor floxed animals. Insulin receptor knockdown led to decreased fat pad mass, morphological and molecular changes in the targeted depot. These novel hybrid AAV vectors can serve as powerful tools to genetically manipulate adipose tissue and provide valuable vehicles to gene therapy targeting adipose tissue.
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University ; The Comprehensive Cancer Center, The Ohio State University.
Xianglan
X
Liu
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University ; The Comprehensive Cancer Center, The Ohio State University.
Daniel
D
Magee
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University ; The Comprehensive Cancer Center, The Ohio State University.
Chuansong
C
Wang
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University ; The Comprehensive Cancer Center, The Ohio State University.
Travis
T
McMurphy
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University ; The Comprehensive Cancer Center, The Ohio State University.
Andrew
A
Slater
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University ; The Comprehensive Cancer Center, The Ohio State University.
Matthew
M
During
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University ; The Comprehensive Cancer Center, The Ohio State University.
Lei
L
Cao