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Mol Ther Methods Clin Dev. 2017 Jun 19;6:68-78. doi: 10.1016/j.omtm.2017.06.002. eCollection 2017 Sep 15.

Targeting Visceral Fat by Intraperitoneal Delivery of Novel AAV Serotype Vector Restricting Off-Target Transduction in Liver.

Huang W1,2, Liu X1,2, Queen NJ1,2, Cao L1,2.

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Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA.
The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.


It is challenging to genetically manipulate fat in adults. We demonstrate that intraperitoneal (i.p.) injection of an engineered adeno-associated virus (AAV) serotype Rec2 leads to high transduction of multiple visceral fat depots at a dose of 1 to 2 orders lower than commonly used doses for systemic gene delivery. To target adipose tissue, we develop a single AAV vector harboring two expression cassettes: one using the CBA promoter to drive transgene expression and one using the liver-specific albumin promoter to drive a microRNA-targeting WPRE sequence that only exists in this AAV vector. This dual-cassette vector achieves highly selective transduction of visceral fat while severely restricting off-target transduction of liver. As proof of efficacy, i.p. administration of an adipose-targeting Rec2 vector harboring the leptin gene corrects leptin deficiency, obesity, and metabolic syndromes of ob/ob mice. This study provides a powerful tool to genetically manipulate fat for basic research and gene therapies of genetic and acquired diseases.


AAV; gene transfer; leptin deficiency; liver restricting; metabolic syndromes; obesity; visceral fat

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