Nephrotoxicity of marketed antisense oligonucleotide drugs

IF 6.1 Q1 TOXICOLOGY

Current Opinion in Toxicology Pub Date : 2022-12-01 DOI:10.1016/j.cotox.2022.100373

Hangyu Wu , Aniket Wahane , Feryal Alhamadani , Kristy Zhang , Rajvi Parikh , SooWan Lee , Evan M. McCabe , Theodore P. Rasmussen , Raman Bahal , Xiao-bo Zhong , José E. Manautou

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引用次数: 2

Abstract

The field of antisense oligonucleotide (ASO)-based therapies have been making strides in precision medicine due to their potent therapeutic application. Early successes in treating some genetic diseases are now attributed to an emerging class of antisense drugs. After two decades, the US Food and Drug Administration (FDA) has approved a considerable number of ASO drugs, primarily to treat rare diseases with optimal therapeutic outcomes. However, safety is one of the biggest challenges to the therapeutic utility of ASO drugs. Due to patients' and health care practitioners' urgent demands for medicines for untreatable conditions, many ASO drugs have been approved. However, a complete understanding of the mechanisms of adverse drug reactions (ADRs) and toxicities of ASOs still need to be resolved. The range of ADRs is unique to a specific drug, while few ADRs are common to a section of drugs as a whole. Nephrotoxicity is an important concern that needs to be addressed considering the clinical translation of any drug candidates ranging from small molecules to ASO-based drugs. This article encompasses what is known about the nephrotoxicity of ASO drugs, the potential mechanisms of action(s), and recommendations for future investigations on the safety of ASO drugs.

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市售反义寡核苷酸药物的肾毒性

基于反义寡核苷酸(ASO)的治疗方法由于其强大的治疗应用，在精准医学领域取得了长足的进步。治疗某些遗传疾病的早期成功现在归功于一类新兴的反义药物。20年来，美国食品和药物管理局(FDA)已经批准了相当数量的ASO药物，主要用于治疗具有最佳治疗效果的罕见疾病。然而，安全性是ASO药物治疗效用的最大挑战之一。由于患者和卫生保健从业人员对治疗不治之症的药物的迫切需求，许多ASO药物已被批准。然而，对ASOs的药物不良反应(adr)和毒性机制的全面了解仍有待解决。不良反应的范围是特定药物所特有的，而少数不良反应是整个药物的一部分所共有的。考虑到从小分子到基于aso的药物的任何候选药物的临床翻译，肾毒性是一个需要解决的重要问题。本文包括ASO药物的肾毒性，潜在的作用机制，以及对未来ASO药物安全性研究的建议。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Opinion in Toxicology Pharmacology, Toxicology and Pharmaceutics-Toxicology

CiteScore

10.40

自引率

0.00%

发文量

期刊介绍： The aims and scope of Current Opinion in Toxicology is to systematically provide the reader with timely and provocative views and opinions of the highest qualified and recognized experts on current advances in selected topics within the field of toxicology. The goal is that Current Opinion in Toxicology will be an invaluable source of information and perspective for researchers, teachers, managers and administrators, policy makers and students. Division of the subject into sections: For this purpose, the scope of Toxicology is divided into six selected high impact themed sections, each of which is reviewed once a year: Mechanistic Toxicology, Metabolic Toxicology, Risk assessment in Toxicology, Genomic Toxicology, Systems Toxicology, Translational Toxicology.