Exploring RNA therapeutics for urea cycle disorders

RNA has triggered a significant shift in modern medicine, providing a promis-ing 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 R...

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Detalles Bibliográficos
Autores: Richard Rodríguez, Eva María, Martínez Pizarro, Ainhoa, Ruiz Desviat, Lourdes
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/715935
Acceso en línea:http://hdl.handle.net/10486/715935
https://dx.doi.org/10.1002/jimd.12807
Access Level:acceso abierto
Palabra clave:Antisense Oligonucleotides
mRNA therapy
Ornithine Transcarbamylase Deficiency
Pseudoexon
Splicing
Urea Cycle
Biología y Biomedicina / Biología
Descripción
Sumario:RNA has triggered a significant shift in modern medicine, providing a promis-ing 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 vac-cines, whose unprecedented worldwide success has meant a definitive boost inthe RNA research field. Urea cycle disorders (UCD), liver diseases with highmortality and morbidity, may benefit from the progress achieved, as differentgenetic 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 theongoing 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 defi-ciency and ornithine transcarbamylase deficiency, in the latter case hasprogressed to the clinical trials phase