Delivery of oligonucleotide-based therapeutics: challenges and opportunities.
Delivery of oligonucleotide-based therapeutics: challenges and opportunities.
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DOI：
10.15252/emmm.202013243
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发表时间：
2021-04-09
影响因子：
11.1
通讯作者：
Arechavala-Gomeza V
中科院分区：
文献类型：
--
作者：
Hammond SM;Aartsma-Rus A;Alves S;Borgos SE;Buijsen RAM;Collin RWJ;Covello G;Denti MA;Desviat LR;Echevarría L;Foged C;Gaina G;Garanto A;Goyenvalle AT;Guzowska M;Holodnuka I;Jones DR;Krause S;Lehto T;Montolio M;Van Roon-Mom W;Arechavala-Gomeza V
几十年来，以核酸为基础的基因表达调控疗法一直以稳定的速度向临床应用发展，但近年来该领域一直在加速发展。迄今为止，有11种基于反义寡核苷酸、适体和小干扰rna的上市产品，还有许多其他产品正在学术界和工业界进行开发。这一发展的一个主要技术触发因素是寡核苷酸化学的进步，以改善药物性质和降低商品成本，但将其应用于更广泛的疾病的主要障碍是向目标组织的递送。诸如缀合物或纳米颗粒等输送技术的采用，已经改变了许多治疗适应症的游戏规则，但许多其他技术仍在等待他们的“尤里卡时刻”。在这里，我们涵盖了各种开发的方法，以提供基于核酸的治疗跨越生物屏障和用于测试它们的模型系统。我们讨论了合成寡核苷酸化学的重要安全考虑和监管要求，以及将实验室突破转化为临床的障碍。本文综述了基于核酸的治疗药物的递送和模型系统的发展的最新进展，以及合成寡核苷酸化学药物的安全性考虑和监管要求。本文综述了基于核酸的治疗药物的递送和模型系统的发展的最新进展，以及合成寡核苷酸化学药物的安全性考虑和监管要求。
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. 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.