2. Academic Validation
  3. Development of a novel anti-inflammatory recombinant uricase with extended half-life for gout therapy

Development of a novel anti-inflammatory recombinant uricase with extended half-life for gout therapy

  • Biochem Biophys Res Commun. 2023 Jul 23:666:115-121. doi: 10.1016/j.bbrc.2023.05.025.
Ziang Zhang 1,  Nannan Fu 1,  Qinkai Li 2,  Junmin Quan 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
  • 2 State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China; Shenzhen Bay Laboratory, Shenzhen, 518055, China. Electronic address: [email protected].
  • 3 State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China. Electronic address: [email protected].
PMID: 37182286 DOI: 10.1016/j.bbrc.2023.05.025
Abstract

Gout is a form of inflammatory arthritis that results from elevated serum uric acid levels and the deposition of urate crystals in multiple joints. The inflammatory response during an acute gout attack is mediated by the activation of the NLRP3 inflammasome, leading to the release of IL-1β and inducing a localized tissue inflammatory response. Urate lowering therapies such as Pegloticase effectively reduce serum uric acid levels but are generally associated with an increase in acute gout flares. In this study, we developed a long-acting anti-inflammatory recombinant uricase by sequential fusing interleukin-1 receptor antagonist (IL-1RA) and albumin-binding domain (ABD) with the N-terminal end of Arthrobacter globiformis uricase (AgUox). The recombinant uricase has longer in vivo half-life, and significantly alleviates monosodium urate (MSU) crystals induced inflammation in mouse model compared with the wild-type AgUox. This long-acting anti-inflammatory recombinant uricase has the potential to be developed as an effective urate lowering therapy with better safety profiles.

Keywords

Albumin-binding domain; Gout; IL-1Ra; Uric acid; Uricase.

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