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Gene therapy

Gene therapy reduced obesity and reversed type 2 diabetes in mice

Fabp4 repression resulted in a 20% reduction of body weight and improved insulin resistance and inflammation after just six weeks of treatment

Researchers from Hanyang University, Seoul, in South Korea, have successfully developed a gene therapy that specifically reduced fat tissue and reversed obesity-related metabolic disease in obese mice. To overcome the side effects of current anti-obesity drugs, researcher Dr Jee Young Chung and colleagues developed a specific gene silencing therapy against a fatty acid metabolism gene, Fabp4.

The outcomes were published in the paper, 'Targeted delivery of CRISPR interference system against Fabp4 to white adipocytes ameliorates obesity, inflammation, hepatic steatosis, and insulin resistance', published in Genome Research.

They used a clustered regularly interspaced short palindromic repeats (CRISPR) interference system wherein catalytically dead Cas9 protein and single guide RNA was targeted to white adipocytes with a tissue-specific fusion peptide. The complex is internalised with little toxicity to the cells and upon internalisation, the molecule complex decreases the expression of Fabp4 and reduces lipid storage in adipocytes.

Demonstrating that this delivery method performed well in cells, Chung and colleagues tested their therapy on obese mice. Mice were fed a diet high in fat leading to obesity and insulin resistance. Fabp4 repression resulted in a 20% reduction of body weight and improved insulin resistance and inflammation after just six weeks of treatment. Additional systemic improvements were observed, including a reduction in fatty lipid deposition in the liver and reduced circulating triglycerides.

“Targeted delivery of the CRISPRi system against Fabp4 to white adipocytes by ATS-9R induced effective silencing of Fabp4, resulting in reduction of body weight and inflammation and restoration of hepatic steatosis in obese mice,” the authors concluded. “This RNA-guided DNA recognition platform provides a simple and safe approach to regress and treat obesity and obesity-induced metabolic syndromes.”

However, while this therapy displays promising results in mice, further studies are required before it can be used in clinical treatment in humans. Importantly, this work highlights the advances in precision gene editing technology, which can be translated to other types of therapies.

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