CRISPR Technology Reactivates Ancient Gene to Combat Gout and Fatty Liver

Researchers at Georgia State University have made significant strides in combating gout and fatty liver disease using CRISPR technology. They have successfully reactivated an ancient gene, uricase, that disappeared from the human lineage millions of years ago.

Gout, which is characterized by intense swelling and pain due to the formation of sharp crystals in joints, has been one of the oldest documented illnesses in humans. The study published in Scientific Reports reveals that by restoring the uricase gene, researchers were able to lower uric acid levels in human liver cells.

Uric acid is a waste product that can crystallize and lead to gout, kidney disease, and other health issues. Interestingly, while most animals retain this gene, humans and other apes lost it roughly 20 to 29 million years ago.

Some experts believe this loss may have provided early primates with a survival advantage by helping them convert fruit sugars into fat during lean times. However, this adaptation has now contributed to various modern metabolic problems.

Professor Eric Gaucher and his team aimed to explore the potential of reactivating the broken uricase gene. Using CRISPR-Cas9, they inserted a reconstructed version of the uricase gene into human liver cells, leading to a surprising drop in uric acid levels and preventing fat accumulation in response to fructose exposure.

They advanced their research to more complex models, using 3D liver spheroids that mimic actual organ function. The reintroduced uricase gene not only reduced uric acid but also functioned correctly within cellular compartments, indicating potential safety in living organisms.

The implications extend beyond gout. High uric acid levels, known as hyperuricemia, are linked to hypertension and cardiovascular disease, with overlapping statistics showing that a significant percentage of individuals with high blood pressure also have elevated uric acid levels.

Gaucher emphasized the dangers of hyperuricemia, suggesting that lowering uric acid could prevent multiple diseases. Current gout treatments are not universally effective, and some patients suffer adverse reactions to existing medications.

The CRISPR method proposed could offer a direct solution, allowing patients to live gout-free lives and potentially preventing fatty liver disease. Future steps involve animal studies and, if successful, human trials.

Possible delivery methods include injections or returning modified liver cells to patients. However, challenges remain, particularly regarding safety and ethical discussions about access to genome editing technology.