Delivery of oligonucleotide‐based therapeutics: challenges and opportunities
Top Cited Papers
Open Access
- 6 April 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 13 (4), e13243
- https://doi.org/10.15252/emmm.202013243
Abstract
Nucleic acid‐based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties and reduce cost of goods, but the main hurdle for the application to a wider range of disorders is delivery to target tissues. The adoption of delivery technologies, such as conjugates or nanoparticles, has been a game changer for many therapeutic indications, but many others are still awaiting their eureka moment. Here, we cover the variety of methods developed to deliver nucleic acid‐based therapeutics across biological barriers and the model systems used to test them. We discuss important safety considerations and regulatory requirements for synthetic oligonucleotide chemistries and the hurdles for translating laboratory breakthroughs to the clinic. Recent advances in the delivery of nucleic acid‐based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide‐based therapeutics.Keywords
Funding Information
- Ikerbasque, Basque Foundation for Science
- Duchenne Parent Project
- Stichting Retina Fonds (UZ2015‐31)
- Ministerio de Ciencia e Innovación (PID2019‐105344RB‐I00)
- Eesti Teadusagentuur (grant PSG226)
- Muscular Dystrophy UK (19GRO‐PG36‐0294)
This publication has 219 references indexed in Scilit:
- Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo**Angewandte Chemie, 2012
- Alginate: Properties and biomedical applicationsProgress in Polymer Science, 2012
- Antisense Oligonucleotide (AON)-based Therapy for Leber Congenital Amaurosis Caused by a Frequent Mutation in CEP290Molecular Therapy Nucleic Acids, 2012
- Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation studyThe Lancet, 2011
- Targeted Delivery of RNAi Therapeutics With Endogenous and Exogenous Ligand-Based MechanismsMolecular Therapy, 2010
- Preclinical PK and PD Studies on 2′-O-Methyl-phosphorothioate RNA Antisense Oligonucleotides in the mdx Mouse ModelMolecular Therapy, 2010
- Rational Design of Antisense Oligomers to Induce Dystrophin Exon SkippingMolecular Therapy, 2009
- A combinatorial library of lipid-like materials for delivery of RNAi therapeuticsNature Biotechnology, 2008
- Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined FactorsCell, 2007
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006