| Sumario: | Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a
potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a
novel targeted, non-viral approach to gene therapy, to deliver genes in the BAT differentiation pathway into rodent SKM to
engineer a thermogenic BAT phenotype with ectopic mUCP-1 overexpression. In parallel, we performed a second protocol
using wild-type Ucp-1-null knockout mice to test whether the effects of the gene therapy are UCP-1 dependent. Our main
findings were a robust cellular presence of mUCP-1 immunostaining (IHC), significantly higher expression levels of mUCP1 measured by qRT-PCR, and highest temperature elevation measured by infrared thermography in the treated thigh,
achieved in rats after delivering the UTMD-PRDM16/PGC-1a/BMP7/hyPB gene cocktail. Interestingly, the weight loss
obtained in the treated rats with the triple gene delivery, never recovered the levels observed in the controls in spite of food
intake recovery. Our results establish the feasibility of minimally invasive UTMD gene-based therapy administration in
SKM, to induce overexpression of ectopic mUCP-1 after delivery of the thermogeni
|
|---|
