Scientists at Georgia State University have used CRISPR gene-editing technology to restore a gene lost by humans millions of years ago, offering a potential new way to treat gout and fatty liver disease.
In research published in Scientific Reports, the team reintroduced uricase, an enzyme that most animals still possess but humans and other apes lost between 20 and 29 million years ago. Uricase helps break down uric acid—a waste product that can form crystals in joints and kidneys when levels get too high, leading to gout, kidney disease, and other health problems.
The evolutionary loss of the uricase gene may have helped early primates survive food shortages by converting fruit sugar into fat more efficiently. However, higher uric acid levels are now linked with modern diseases. Eric Gaucher, biology professor at Georgia State University and co-author of the study, explained their motivation: “Without uricase, humans are left vulnerable,” said Gaucher. “We wanted to see what would happen if we reactivated the broken gene.”
Working with postdoctoral researcher Lais de Lima Balico, Gaucher’s team inserted a reconstructed ancient uricase gene into human liver cells using CRISPR-Cas9 technology. The modified cells showed lower uric acid levels and did not accumulate fat from fructose intake. To further test their findings beyond simple cell cultures, researchers introduced the revived gene into 3D liver spheroids—miniature lab-grown tissues that simulate real organ behavior—and observed similar reductions in uric acid.
“By reactivating uricase in human liver cells, we lowered uric acid and stopped the cells from turning excess fructose into triglycerides — the fats that build up in the liver,” Gaucher said.
Elevated uric acid is associated not only with gout but also with conditions like hypertension and cardiovascular disease. Studies indicate that about 25% to 50% of patients with high blood pressure also show elevated uric acid; for newly diagnosed hypertension cases, this overlap rises to 90%.
“Hyperuricemia is a dangerous condition,” said Gaucher. “By lowering uric acid, we could potentially prevent multiple diseases at once.”
Current therapies for gout do not work for all patients; some experience adverse reactions to synthetic forms of uricase. The CRISPR-based approach could offer an alternative by restoring natural production within patients’ own liver cells.
“Our genome-editing approach could allow patients to live gout-free lives and potentially prevent fatty liver disease,” Gaucher said.
The next steps include animal studies followed by human trials if results continue to be positive. Potential delivery methods being considered range from direct injections or transplantation of modified cells to using lipid nanoparticles—similar to those utilized in certain COVID-19 vaccines—to deliver genetic material.
Gaucher cautioned about ongoing challenges: “Genome-editing still faces substantial safety concerns,” he said. “Once those are addressed, society will be faced with contentious ethical discussions about who should and should not have access.”
