Evolution of antisense oligonucleotides: navigating nucleic acid chemistry and delivery challenges.

IF 6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert Opinion on Drug Discovery Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI:10.1080/17460441.2024.2440095

Ruchi Ruchi, Govind Mukesh Raman, Vikas Kumar, Raman Bahal

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引用次数: 0

Abstract

Introduction: Antisense oligonucleotide (ASO) was established as a viable therapeutic option for genetic disorders. ASOs can target RNAs implicated in various diseases, including upregulated mRNA and pre-mRNA undergoing abnormal alternative splicing events. Therapeutic applications of ASOs have been proven with the Food and Drug Administration approval of several drugs in recent years. Earlier enzymatic stability and delivery remains a big challenge for ASOs. Introducing new chemical modifications and new formulations resolving the issues related to the nuclease stability and delivery of the ASOs. Excitingly, ASOs-based bioconjugates that target the hepatocyte have gained much attraction. Efforts are ongoing to increase the therapeutic application of the ASOs to the extrahepatic tissue as well.

Area covered: We have briefly discussed the mechanism of ASOs, the development of new chemistries, and delivery strategies for ASO-based drug discovery and development. The discussion focuses more on the already approved ASOs and those in the clinical development stage.

Expert opinion: To expand the clinical application of ASOs, continuous effort is required to develop precise delivery strategies for targeting extrahepatic tissue to minimize the off-target effects.

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来源期刊

Expert Opinion on Drug Discovery 医学-药学

CiteScore

10.20

自引率

1.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.