A stable liver-specific urate oxidase gene knockout hyperuricemia mouse model finds activated hepatic de novo purine biosynthesis and urate nephropathy

Pang, Lei; Liang, Ningning; Li, Changgui; Merriman, Tony R.; Zhang, Hui; Yan, Fei; Sun, Wenyan; Li, Rui; Xue, Xiaomei; Liu, Zhen; Wang, Can; Cheng, Xiaoyu; Chen, Shiting; Yin, Huiyong; Dalbeth, Nicola; Yuan, Xuan

doi:10.1016/j.bbadis.2023.167009

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

2024

DOI: 10.1016/j.bbadis.2023.167009

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A stable liver-specific urate oxidase gene knockout hyperuricemia mouse model finds activated hepatic de novo purine biosynthesis and urate nephropathy

Lei Pang,

Ningning Liang,

Changgui Li

et al.

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Cited by 3 publications

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Natural polysaccharides in the prevention of hyperuricemia: Source, classification, mechanism, application in food industry

Ren,

Dang,

Wang

et al. 2025

International Journal of Biological Macromolecules

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Natural polysaccharides in the prevention of hyperuricemia: Source, classification, mechanism, application in food industry

Ren,

Dang,

Wang

et al. 2025

International Journal of Biological Macromolecules

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Atavistic strategy for the treatment of hyperuricemia via ionizable liposomal mRNA

Zhang,

Hussain,

et al. 2024

Nat Commun

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Hyperuricemia is associated with an increased risk of gout, hypertension, diabetes, and cardiovascular diseases. Most mammals maintain normal serum uric acid (SUA) via urate oxidase (Uox), an enzyme that metabolizes poorly-soluble UA to highly-soluble allantoin. In contrast, Uox became a pseudogene in humans and apes over the long course of evolution. Here we demonstrate an atavistic strategy for treating hyperuricemia based on endogenous expression of Uox in hepatocytes mediated by mRNA (mUox) loaded with an ionizable lipid nanoparticle termed iLAND. mUox@iLAND allows effective transfection and protein expression in vitro. A single dose of mUox@iLAND lowers SUA levels for several weeks in two female murine models, including a novel long-lasting model, which is also confirmed by metabolomics analysis. Together with the excellent safety profiles observed in vivo, the proposed mRNA agent demonstrates substantial potential for hyperuricemia therapy and the prevention of associated conditions.

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Preparation and Efficacy Evaluation of Antihyperuricemic Peptides from Marine Sources

Qiao,

Huang,

Sun

et al. 2024

Nutrients

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Marine-derived foods, often called blue foods, are promising sustainable alternatives to conventional food sources owing to their abundant amino acids and high protein content. Current treatments for hyperuricemia, a chronic condition attributed to purine metabolism disorders, are associated with various side effects. Novel peptide xanthine oxidase inhibitors have been discovered in the hydrolyzed products of marine fish and invertebrate proteins, which have demonstrated promising therapeutic potential by reducing uric acid levels in vitro and in vivo. This review explores the potential therapeutic effects of xanthine oxidase inhibitors derived from marine fish and invertebrates, summarizes the methods for extracting bioactive peptides from marine organisms, and emphasizes the impact of different proteases on the structure–activity relationship of bioactive peptides. The hypouricemic effects of these bioactive peptides warrant further verification. There is consensus on the in vitro chemical methods used to verify the xanthine oxidase inhibitory effects of these peptides. Considering several cell and animal model development strategies, this review summarizes several highly recognized modeling methods, proposes strategies to improve the bioavailability of bioactive peptides, and advocates for a diversified evaluation system. Although the screening and evaluation methods for antihyperuricemic peptides have been shown to be feasible across numerous studies, they are not optimal. This review examines the deficiencies in bioavailability, synthesis efficiency, and evaluation mechanisms in terms of their future development and proposes potential solutions to address these issues. This review provides a novel perspective for the exploration and application of marine-derived hypouricemic bioactive peptides.

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A stable liver-specific urate oxidase gene knockout hyperuricemia mouse model finds activated hepatic de novo purine biosynthesis and urate nephropathy

Cited by 3 publications

References 45 publications

Natural polysaccharides in the prevention of hyperuricemia: Source, classification, mechanism, application in food industry

Natural polysaccharides in the prevention of hyperuricemia: Source, classification, mechanism, application in food industry

Atavistic strategy for the treatment of hyperuricemia via ionizable liposomal mRNA

Preparation and Efficacy Evaluation of Antihyperuricemic Peptides from Marine Sources

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