Exploring RNA therapeutics for urea cycle disorders.

Autor: Richard E; Centro de Biología Molecular Severo Ochoa UAM-CSIC, IUBM, CIBERER, IdiPaz, Universidad Autónoma de Madrid, Madrid, Spain., Martínez-Pizarro A; Centro de Biología Molecular Severo Ochoa UAM-CSIC, IUBM, CIBERER, IdiPaz, Universidad Autónoma de Madrid, Madrid, Spain., Desviat LR; Centro de Biología Molecular Severo Ochoa UAM-CSIC, IUBM, CIBERER, IdiPaz, Universidad Autónoma de Madrid, Madrid, Spain.
Jazyk: angličtina
Zdroj: Journal of inherited metabolic disease [J Inherit Metab Dis] 2024 Nov; Vol. 47 (6), pp. 1269-1277. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1002/jimd.12807
Abstrakt: RNA has triggered a significant shift in modern medicine, providing a promising way to revolutionize disease treatment methods. Different therapeutic RNA modalities have shown promise to replace, supplement, correct, suppress, or eliminate the expression of a targeted gene. Currently, there are 22 RNA-based drugs approved for clinical use, including the COVID-19 mRNA vaccines, whose unprecedented worldwide success has meant a definitive boost in the RNA research field. Urea cycle disorders (UCD), liver diseases with high mortality and morbidity, may benefit from the progress achieved, as different genetic payloads have been successfully targeted to liver using viral vectors, N-acetylgalactosamine (GalNAc) conjugations or lipid nanoparticles (LNP). This review explores the potential of RNA-based medicines for UCD and the ongoing development of applications targeting specific gene defects, enzymes, or transporters taking part in the urea cycle. Notably, LNP-formulated mRNA therapy has been assayed preclinically for citrullinemia type I (CTLN1), adolescent and adult citrin deficiency, argininosuccinic aciduria, arginase deficiency and ornithine transcarbamylase deficiency, in the latter case has progressed to the clinical trials phase.
(© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze: MEDLINE
Externí odkaz: