小核酸类药物的修饰和靶向递送研究进展

Research progress on modification and targeted delivery of small nucleic acid drugs

小核酸类药物是在基因水平上发挥作用的小RNA分子,包括小干扰RNA、反义寡核苷酸、核酸适配体、微RNA等。小核酸类药物研发中面临易被核酸酶降解、半衰期短、易被血液循环中的免疫细胞识别、跨膜转运困难等难题。利用化学修饰和末端修饰可提高小核酸的抗酶解能力和稳定性,延长半衰期,降低免疫原性,提高靶向性。利用核酸类药物载体可协助核酸类药物到达病灶,增加靶向性,并实现溶酶体逃逸,提高药效。常用的载体包括病毒载体、脂质体、无机纳米粒子、聚合物纳米粒子和外泌体等。本文综述小核酸药物的修饰和递送技术研究进展,探讨提高小核酸类药物药效和靶向性的策略,以期为小核酸类药物的临床应用转化提供参考。

Small nucleic acid drugs are small RNA molecules that act at the genetic level,including small interfering RNA,antisense oligonucleotides,nucleic acid aptamers,microRNA,etc.In the development of small nucleic acid drugs,there are challenges such as susceptibility to degradation by nucleases,short half-life,susceptibility to immune recognition in the bloodstream,and difficulty in transmembrane transport.The use of chemical and terminal modifications can enhance the anti enzymatic ability and stability of small nucleic acids,prolong their half-life,reduce immunogenicity,and improve targeting.The use of nucleic acid drug carriers can assist nucleic acid drugs in reaching lesions,increase targeting,and achieve lysosomal escape,thereby improving drug efficacy.Common carriers include viral vectors,liposomes,inorganic nanoparticles,polymer nanoparticles,and exosomes.This article reviews the research progress on modification and delivery technology of small nucleic acid drugs,and explores strategies to improve the efficacy and targeting of small nucleic acid drugs,in order to provide reference for the clinical application and translation of small nucleic acid drugs.