Microbial uricase enzymes in hyperuricemia management: Sources, challenges, and technological advances

The downregulation of uric acid within the human body is intricately governed by the urate oxidase enzyme. This enzyme activity is notably present in various sources including microbial, plant, and certain animal origins. The normal concentration of uric acid in healthy individuals ranges from 3 to 6 mg/dl. However, abnormal conditions such as a high purine diet and tumor lysis syndrome can lead to elevated uric acid levels, constituting a primary etiological factor for hyperuricemia and gout. Recombinant uricases, such as rasburicase and pegloticase, have emerged as therapeutic interventions, effectively mitigating the severity of gout. Nonetheless, their utilization is constrained by immunogenicity and a relatively short half-life. Consequently, there is a compelling need for novel uricase variants characterized by lower immunogenicity and enhanced stability. This review aims to delineate alternative sources of uricase, elucidate their physico-chemical properties and clinical implications, and provide comprehensive insights into the potential of recombinant uricase. The significance of genetically modified uricase and polyethylene glycol (PEG)-conjugated uricase as highly promising treatment modalities for gout is emphasized. The application of uricase-based nanosensors, chips, biosensors, and nanocomposites for facile uric acid detection in samples is also highlighted. Given its considerable potential, uricase stands as a promising tool in the clinical realm for treating gouty and hyperuricemic conditions.