Bioorganic Chemistry Laboratory, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Aichi, 464-0813, Japan.
Bioorganic Chemistry Laboratory, Graduate School of Science, Nagoya University, Chikusa-Ku, Nagoya, Aichi, 464-8602, Japan.
Chembiochem. 2020 Jul 1;21(13):1808-1815. doi: 10.1002/cbic.202000009. Epub 2020 May 18.
There is great potential for siRNA in the treatment of diseases through the reduction of damaging protein translation by RNA interference. However, the delivery and cell uptake of siRNA pose a serious problem in its therapeutic application. Methods to overcome this issue include chemical modification of the siRNA duplex to improve pharmacokinetics, stability and efficacy, and conjugation to small ligand molecules to enable membrane penetration, targetability and potency. In this review, the most common modifications of siRNA will be discussed, along with ligand conjugates that are believed to be the most promising in advancing the field of targeted siRNA delivery.
通过 RNA 干扰减少有害蛋白翻译，siRNA 在疾病治疗方面具有巨大潜力。然而，siRNA 的递释和细胞摄取在其治疗应用中构成严重问题。克服这一问题的方法包括对 siRNA 双链体进行化学修饰以改善药代动力学、稳定性和功效，以及与小分子配体缀合以实现膜穿透、靶向性和效力。在本综述中，将讨论 siRNA 的最常见修饰以及配体缀合物，这些修饰和缀合物被认为在推进靶向 siRNA 递释领域最有前途。
