CRISPR Reactivates Ancient Gene to Combat Gout and Fatty Liver

Researchers at Georgia State University have made a significant breakthrough using CRISPR technology to reactivate an ancient gene known as uricase, which has implications for treating gout and fatty liver disease.

According to a study published in Scientific Reports, gout, a form of arthritis caused by the crystallization of uric acid in joints, is one of the oldest documented human illnesses. The uricase enzyme, which is still present in most other animals, breaks down uric acid, a waste product that can lead to various health issues when accumulated.

Interestingly, humans lost the uricase gene approximately 20 to 29 million years ago, a change that some researchers believe may have provided early primates with a survival advantage by aiding in fat storage.

However, today, this loss contributes to modern metabolic disorders, prompting Georgia State biology professor Eric Gaucher and his team to investigate the potential benefits of reactivating this gene.

Using CRISPR-Cas9, they were able to insert a reconstructed version of the uricase gene into human liver cells, which resulted in significantly lowered uric acid levels and prevented fat accumulation in the cells when exposed to fructose.

The team then tested the gene in 3D liver spheroids, which more closely mimic actual organ function, and again saw reduced uric acid levels, with the enzyme functioning appropriately in the designated cellular compartments.

Gaucher noted that the implications of high uric acid levels extend beyond gout; hyperuricemia has been linked to hypertension and cardiovascular disease, with a notable overlap between high blood pressure and elevated uric acid levels.

Current treatments for gout often prove ineffective or produce adverse reactions, but a CRISPR approach to restore uricase directly in liver cells could provide a safer and more effective alternative. If these findings are validated in animal studies and subsequently in human trials, this innovative gene-editing technique could reshape the treatment landscape for gout and related metabolic disorders.

The researchers are considering various delivery methods for this gene therapy, including direct injections or leveraging lipid nanoparticles similar to those used in COVID-19 vaccines. However, Gaucher cautioned that safety concerns remain a significant hurdle, and societal ethics regarding access to such treatments will need to be addressed.

Despite these challenges, this research marks a pivotal step toward utilizing CRISPR technology in treating complex metabolic issues effectively.