Gene Therapy Reduces Obesity, Inflammation, Hepatic Steatosis and Insulin Resistance¹

Obesity is an ongoing pathophysiological problem throughout various societies. A CRISPR interference (CRISPRi) mechanism based on catalytically dead Cas9 (dCas9) and single guide RNA (sgRNA) were both combined with a targeted non-viral gene to treat obesity and obesity-induced T2DM. A fatty acid metabolism gene, Fabp4, in white adipocytes was targeted and as a result, there was a decrease in Fabp4 expression and reduced lipid storage in adipocytes. The therapy was also tested on obese mice, where a high-fat was given. After six weeks of treatment it was observed that Fabp4 repression resulted in a 20% reduction of body weight, improved insulin resistance and inflammation, a reduction in fatty lipid deposition in the liver and reduced circulating triglycerides.

References

1. Chung JY, et al. Genome Res 2019;29:1442-1452.