Back to Search
Start Over
Atavistic strategy for the treatment of hyperuricemia via ionizable liposomal mRNA.
- Source :
-
Nature communications [Nat Commun] 2024 Jul 31; Vol. 15 (1), pp. 6463. Date of Electronic Publication: 2024 Jul 31. - Publication Year :
- 2024
-
Abstract
- 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Mice
Humans
Nanoparticles chemistry
Hepatocytes metabolism
Disease Models, Animal
Mice, Inbred C57BL
Hyperuricemia drug therapy
Hyperuricemia genetics
Hyperuricemia metabolism
RNA, Messenger metabolism
RNA, Messenger genetics
Urate Oxidase metabolism
Urate Oxidase genetics
Uric Acid metabolism
Uric Acid blood
Liposomes chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39085241
- Full Text :
- https://doi.org/10.1038/s41467-024-50752-9