Exploring RNA therapeutics for urea cycle disorders.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Inherited Metabolic Disease Pub Date : 2024-10-24 DOI:10.1002/jimd.12807
Eva Richard, Ainhoa Martínez-Pizarro, Lourdes R Desviat
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Abstract

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.

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探索治疗尿素循环障碍的 RNA 疗法。
RNA 引发了现代医学的重大变革,为彻底改变疾病治疗方法提供了一条大有可为的途径。不同的 RNA 治疗模式已显示出取代、补充、纠正、抑制或消除目标基因表达的前景。目前,已有 22 种基于 RNA 的药物获准用于临床,其中包括 COVID-19 mRNA 疫苗。尿素循环障碍(UCD)是死亡率和发病率都很高的肝脏疾病,它可能会从已取得的进展中受益,因为不同的基因载荷已通过病毒载体、N-乙酰半乳糖胺(GalNAc)连接或脂质纳米颗粒(LNP)成功靶向肝脏。本综述探讨了基于 RNA 的药物治疗尿毒症的潜力,以及针对参与尿素循环的特定基因缺陷、酶或转运体的应用的不断发展。值得注意的是,针对瓜氨酸血症 I 型 (CTLN1)、青少年和成人瓜氨酸缺乏症、精氨酸琥珀酸尿症、精氨酸酶缺乏症和鸟氨酸转氨酶缺乏症的 LNP 配方 mRNA 治疗已进行了临床前试验,其中鸟氨酸转氨酶缺乏症已进入临床试验阶段。
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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
期刊最新文献
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