Institute of Molecular Health Sciences, ETH Zurich, Zürich, Switzerland.
Medical Faculty, University of Zürich, Zürich, Switzerland.
Nat Rev Drug Discov. 2022 Jun;21(6):417-439. doi: 10.1038/s41573-022-00407-5. Epub 2022 Feb 24.
Recent years have seen unprecedented activity in the development of RNA-silencing oligonucleotide therapeutics for metabolic diseases. Improved oligonucleotide design and optimization of synthetic nucleic acid chemistry, in combination with the development of highly selective and efficient conjugate delivery technology platforms, have established and validated oligonucleotides as a new class of drugs. To date, there are five marketed oligonucleotide therapies, with many more in clinical studies, for both rare and common liver-driven metabolic diseases. Here, we provide an overview of recent developments in the field of oligonucleotide therapeutics in metabolism, review past and current clinical trials, and discuss ongoing challenges and possible future developments.
近年来，代谢疾病的 RNA 沉默寡核苷酸治疗药物的研发活动空前活跃。改进的寡核苷酸设计和合成核酸化学的优化，结合高效选择性和高效共轭递药技术平台的发展，已经确立并验证了寡核苷酸作为一种新的药物类别。迄今为止，已有五种市售的寡核苷酸疗法，还有更多的用于治疗罕见和常见的肝脏驱动代谢疾病的寡核苷酸疗法正在临床研究中。在此，我们概述了代谢领域中寡核苷酸治疗的最新进展，回顾了过去和当前的临床试验，并讨论了正在面临的挑战和可能的未来发展。
