The Potential of an19 Synthetic Uricase as a Therapeutic for Gout

Most mammals produce the enzyme uricase to convert uric acid in the blood to more-soluble allantoin before excretion, but uricase in humans is not functional. This leads humans to develop high concentrations of uric acid in their blood, resulting in health complications such as gout. Currently, there are no adequate treatments on the market. Our lab used Ancestral Sequence Reconstruction (ASR) and protein engineering to resurrect an ancestral uricase called an19. I administered an19 to uricase-knockout mice at enzymatic units ranging from 0.1-0.2 weekly for 8 weeks via retro-orbital injection. Blood and urine samples were collected 4 hours after injection, and the effect of the uricase was measured through colorimetric assays on those samples. If this modified uricase can lower uric acid in the bloodstream, it could be a new treatment route for those suffering from gouty arthritis.