Gene delivery to adipose tissue using novel recombinant adeno-associated viral (AAV) vectors
T2017-118 An engineered recombinant adeno-associated virus capable of targeting visceral fat tissue for the purposes of genetic manipulation.
Recombinant adeno-associated viruses (rAAVs) are effective tools for delivering gene therapy treatment and for manipulation of acquired diseases. However, there is no effective method to target adipose tissue and transduction efficiency is low in naturally occurring AAV serotypes. In addition, current methods of gene therapy can result in off-target transgene expression. New high transduction, effective viral vectors that avoid detrimental, off-target effects and are capable of genomic delivery exclusively to adipose tissue are needed.
Researchers at The Ohio State University have developed a unique approach using novel rAAV expression plasmids to efficiently deliver genes to adipose tissue while severely restricting off-target expression in liver. This technology provides a vehicle to genetically manipulate adipose for basic research, as well as treat genetic and acquired diseases such as obesity, metabolic syndromes, and cancer.
For instance, patients with a genetic defect in leptin are obese and require life-long treatment of leptin, a hormone produced primarily in adipose tissue. This technology has been shown to rescue mice with leptin deficiencies, wherein AS/Rec2-leptin treatment completely prevented weight gain and normalized body weight close to age-matched WT mice. AS/Rec2-leptin treatment also completely rescued the impaired glycemic control of ob/ob mice. Additionally, this technology has been shown to modulate the tumor microenvironment iin vivo and significantly affect tumor progression by activating tumor infiltrating NK cells. This invention provides a powerful approach to genetically manipulate adipocytes for modulation of adipose-derived endocrine functions and adipose residing immune cells.
- Gene therapy
- Metabolic syndromes
- Targets a gene therapy to a specific tissue for which there is currently no delivery method
- Lower dose of vector required compared to commonly used systemic gene deliveries
- Expands the capabilities of gene therapy for adipose related health concerns