THE LONG-TERM GOAL OF THIS PROJECT IS TO DEVELOP A THERA- PEUTIC URICASE THAT CAN BE USED IN HYPERURICEMIA AND THE VARIOUS MANIFESTATIONS OF GOUT, INCLUDING ACUTE AND CHRONIC GOUTY ARTHRITIS TOPHI AND URATE DEPOSITS IN TISSUES AND ORGANS, AND URIC ACID

THE LONG-TERM GOAL OF THIS PROJECT IS TO DEVELOP A THERA- PEUTIC URICASE THAT CAN BE USED IN HYPERURICEMIA AND THE VARIOUS MANIFESTATIONS OF GOUT, INCLUDING ACUTE AND CHRONIC GOUTY ARTHRITIS TOPHI AND URATE DEPOSITS IN TISSUES AND ORGANS, AND URIC ACID NEPHROPATHY. IT IS EXPECTED THAT THE THERAPEUTIC URICASE WILL BE ABLE TO COMPLETELY REMOVE URATE DEPOSITS IN THE BODY. IT WILL ALSO CONTROL HYPERURICEMIA IFGIVEN AT INTERVALS IN SMALL AMOUNTS. THERAPEUTIC URICASE SHOULD BE ABLE TO DISSOLVE URATE DEPOSITS IN A MATTER OF HOURS OR DAYS, AND SHOULD PROVIDE IMMEDIATE RELIEF FOR ACUTEGOUTY ARTHRITIS ATTACKS, WITH NO LIKELIHOOD OF RECURRENCE. CANCER PATIENTS UNDERGOING AGGRESSIVE RADIATION OR CHEMO- THERAPY AGAINST LARGE TUMOR MASSES WILL BE PROTECTED FROM EXCESSIVE URATE PRODUCTION. THE SPECIFIC AIMS OF THIS PROJECT ARE TO MODIFY BY COVALENT ATTACHMENT OF MONOMETHOXY-POLYETHYLENE GLYCOL (PEG) A SELECTED URICASE WITH HIGH ACTIVITY, GOOD STABILITY, AND CONTROLLED IMMUNOGENICITY. PROCEDURES FOR DEVELOPING A HOMOGENEOUS PEG-URICASE ARE PROCEEDING. ANIMAL TOXICOLOGY STUDIES WILL BE DONE IN MICE,RATS, AND DOGS.