Zhang Lei, Liang Yayu, Liang Guohui, Tian Zhili, Zhang Yue, Liu Zhihui, Ji Xinying
Henan International Joint Laboratory of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, China.
School of Stomatology, Henan University, Kaifeng, China.
Front Pharmacol. 2022 Dec 14;13:1090237. doi: 10.3389/fphar.2022.1090237. eCollection 2022.
RNA interference has become increasingly used for genetic therapy following the rapid development of oligonucleotide drugs. Significant progress has been made in its delivery system and implementation in the treatment of target organs. After a brief introduction of RNA interference technology and siRNA, the efficiency and stability of GalNAc-siRNA conjugates are highlighted since several oligonucleotide drugs of GalNAc have been approved for clinical use in recent years. The structure and features of GalNAc-siRNA conjugates are studied and the clinical efficiency and limitations of oligonucleotide-based drugs are summarized and investigated. Furthermore, another delivery system, lipid nanoparticles, that confer many advantages, is concluded, includ-ing stability and mass production, compared with GalNAc-siRNA conjugates. Importantly, developing new approaches for the use of oligonucleotide drugs brings hope to genetic therapy.
随着寡核苷酸药物的迅速发展，RNA干扰在基因治疗中的应用越来越广泛。其递送系统以及在靶器官治疗中的应用都取得了显著进展。在简要介绍RNA干扰技术和小干扰RNA（siRNA）后，由于近年来几种GalNAc寡核苷酸药物已获批用于临床，因此重点介绍了GalNAc-siRNA偶联物的效率和稳定性。研究了GalNAc-siRNA偶联物的结构和特点，并总结和研究了基于寡核苷酸药物的临床疗效和局限性。此外，还总结了另一种具有许多优势的递送系统——脂质纳米颗粒，与GalNAc-siRNA偶联物相比，其优势包括稳定性和可大规模生产。重要的是，开发寡核苷酸药物的新应用方法为基因治疗带来了希望。
