Uricase Nanoparticles

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Introduction: Elevated uric acid levels can lead to several complications, including hyperuricemia, Gout, Tumor Lysis Syndrome, and Lesch-Nyhan disease. Gout, the most common condition of hyperuricemia, is seen in 3.9% of the U.S. population. In 2016, the prevalence rate of hyperuricemia in the U.S. was estimated at 20%. Human bodies have a functional uricase enzyme to metabolize uric acid and maintain the plasma uric acid levels in the range of 1-2mg/dL. Hyperuricemia occurs when uric acid in blood concentrations is greater than 6.8 mg/dL. Despite many treatment options have been developed for hyperuricemia, side effects can often result in fever, allergic reactions, kidney problem, and in some cases, death due to antibody development against uricase epitopes. In addition, FDA-approved uricase therapeutic Krystexxa elicits strong immune response due to the PEGylation. Thus, there remains a need to develop more robust therapeutics for hyperuricemia without the need for PEGylation to increase stability. Technology: Georgia state researchers and their collaborators have developed nanoparticles composed of viral vesicles that contain ancestral uricase An67 (Qβ-AncUOX vesicles). This uricase enzyme formula is stable while also free of PEGylation, by combining Ancestral Sequence Reconstruction (ASR) and CRISPR engineering. A donor DNA fragment containing uricase “An67” was genomically integrated into HEK293 cells, confirmed in the PCR screenings. In vitro studies show that uricase is expressed in the engineered cells and localized to the peroxisome. Uricase-positive cells exhibit uric acid levels to levels near or even below pre-exposure. In vitro studies also demonstrated that cell lines representing three type of brain tissues and one kidney tissue could transcribe uricase genes.