Expression, localization and metabolic function of “resurrected” human urate oxidase in human hepatocytes

A high serum uric acid (SUA) concentration is associated with hyperuricemia (HUA) and gout. In order to obtain long-acting therapeutic effect, correction of purine metabolism at genetic level is advantageous. For this purpose, we expressed three “human-like” urate oxidases in human hepatocytes (HL-7702) by lentivirus-mediated transduction. Enzymatic assay revealed that the recombinant urate oxidases expressed in HL-7702 cells were functionally active. Electron microscopy study showed that the recombinant enzymes were localized to peroxisome and formed distinct crystalloid core structures as in other mammal cells. Although similar rate of uric acid degradation was observed for all recombinant urate oxidases, HL-7702-pLVX-UOX83 cells and HL-7702-pLVX-UOX214/217 cells retained more cell viability compared with HL-7702-pLVX-UOXPBC at high uric acid level. This study provides a new direction for the treatment of gout and hyperuricemia.