ArticlePloS one2016
A Therapeutic Uricase with Reduced Immunogenicity Risk and Improved Development Properties.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 60 citations in OpenAlex.
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- Stability and functional consequences of disulfide bond engineering in Aspergillus flavus uricase.Scientific reports · 2025Article
- A Multi-Enzyme Nanocascade to Target Disease-Relevant Metabolites.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Dissecting Uricase Immunogenicity: Unveiling the Role of Quaternary Epitopes through In Silico Analysis : Quaternary Epitope Insights in Uricase Immunogenicity.Galen medical journal · 2025Article
- Emerging Urate-Lowering Drugs and Pharmacologic Treatment Strategies for Gout: A Narrative Review.Drugs · 2023Review
- Oral Delivery of Nanoparticles Carrying Ancestral Uricase Enzyme Protects against Hyperuricemia in Knockout Mice.Biomacromolecules · 2023Article
- PASylated Urate Oxidase Enzyme: Enhancing Biocatalytic Activity, Physicochemical Properties, and Plasma Half-Life.ACS omega · 2022Article
- Polyethylene Glycol-Like Brush Polymer Conjugate of a Protein Drug Does Not Induce an Antipolymer Immune Response and Has Enhanced Pharmacokinetics than Its Polyethylene Glycol Counterpart.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Phylogenetic Articulation of Uric Acid Evolution in Mammals and How It Informs a Therapeutic Uricase.Molecular biology and evolution · 2022Article
- Development of Pharmaceutical Nanomedicines: From the Bench to the Market.Pharmaceutics · 2022Review
- The past, present, and future of enzyme-based therapies.Drug discovery today · 2022Review
- The impact of ethnicity and intra-pancreatic fat on the postprandial metabolome response to whey protein in overweight Asian Chinese and European Caucasian women with prediabetes.Frontiers in clinical diabetes and healthcare · 2022Article
- High MW polyethylene glycol prolongs circulation of pegloticase in mice with anti-PEG antibodies.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
- Design of Bacillus fastidious Uricase Mutants Bearing Long Lagging Phases Before Exponential Decreases of Activities Under Physiological Conditions.The protein journal · 2021Article
- Chemical Modification of Cysteine with 3-Arylpropriolonitrile Improves the In Vivo Stability of Albumin-Conjugated Urate Oxidase Therapeutic Protein.Biomedicines · 2021Article
- Thermostable and Long-Circulating Albumin-ConjugatedPharmaceutics · 2021Article
- Molecular Elucidation of a Urate Oxidase fromInternational journal of molecular sciences · 2021Article
- The Effective Control of Hyperuricemia in Cancer Patients: A New Recombinant Conjugated Variant of Urate Oxidase.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Structure-Based Immunogenicity Prediction of Uricase from Fungal (Aspergillus flavus), Bacterial (Bacillus subtillis) and Mammalian Sources Using Immunoinformatic Approach.The protein journal · 2020Article
- Structure-based design of a hyperthermostable AgUricase for hyperuricemia and gout therapy.Acta pharmacologica Sinica · 2019Article
Corrections and comments
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Authors and funding
28 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Humans and higher primates are unique in that they lack uricase, the enzyme capable of oxidizing uric acid. As a consequence of this enzyme deficiency, humans have high serum uric acid levels. In some people, uric acid levels rise above the solubility limit resulting in crystallization in joints, acute inflammation in response to those crystals causes severe pain; a condition known as gout. Treatment for severe gout includes injection of non-human uricase to reduce serum uric acid levels. Krystexxa® is a hyper-PEGylated pig-baboon chimeric uricase indicated for chronic refractory gout that induces an immunogenic response in 91% of treated patients, including infusion reactions (26%) and anaphylaxis (6.5%). These properties limit its use and effectiveness. An innovative approach has been used to develop a therapeutic uricase with improved properties such as: soluble expression, neutral pH solubility, high E. coli expression level, thermal stability, and excellent activity. More than 200 diverse uricase sequences were aligned to guide protein engineering and reduce putative sequence liabilities. A single uricase lead candidate was identified, which showed low potential for immunogenicity in >200 human donor samples selected to represent diverse HLA haplotypes. Cysteines were engineered into the lead sequence for site specific PEGylation and studies demonstrated >95% PEGylation efficiency. PEGylated uricase retains enzymatic activity in vitro at neutral pH, in human serum and in vivo (rats and canines) and has an extended half-life. In canines, an 85% reduction in serum uric acid levels was observed with a single subcutaneous injection. This PEGylated, non-immunogenic uricase has the potential to provide meaningful benefits to patients with gout.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.