College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Zhejiang University Cancer Center, Hangzhou 310058, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Aug 25;52(4):417-428. doi: 10.3724/zdxbyxb-2023-0130.
Nucleic acid-based drugs, such as RNA and DNA drugs, exert their effects at the genetic level. Currently, widely utilized nucleic acid-based drugs include nucleic acid aptamers, antisense oligonucleotides, mRNA, miRNA, siRNA and saRNA. However, these drugs frequently encounter challenges during clinical application, such as poor stability, weak targeting specificity, and difficulties in traversing physiological barriers. By employing chemical modifications of nucleic acid structures, it is possible to enhance the stability and targeting specificity of certain nucleic acid drugs within the body, thereby improving delivery efficiency and reducing immunogenicity. Moreover, utilizing nucleic acid drug carriers can facilitate the transportation of drugs to lesion sites, thereby aiding efficient intracellular escape and promoting drug efficacy within the body. Currently, commonly employed delivery carriers include virus vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers and extracellular vesicles. Nevertheless, individual modifications or delivery carriers alone are insufficient to overcome numerous obstacles. The integration of nucleic acid chemical modifications with drug delivery systems holds promise for achieving enhanced therapeutic effects. However, this approach also presents increased technical complexity and clinical translation costs. Therefore, the development of nucleic acid drug carriers and nucleic acid chemical modifications that are both practical and simple, while maintaining high efficacy, low toxicity, and precise nucleic acid delivery, has become a prominent research focus in the field of nucleic acid drug development. This review comprehensively summarizes the advancements in nucleic acid-based drug modifica-tions and delivery systems. Additionally, strategies to enhance nucleic acid drug delivery efficiency are discussed, with the aim of providing valuable insights for the translational application of nucleic acid drugs.
核酸类药物，如 RNA 和 DNA 药物，在基因水平发挥作用。目前，广泛应用的核酸类药物包括核酸适体、反义寡核苷酸、mRNA、miRNA、siRNA 和 saRNA。然而，这些药物在临床应用中经常遇到挑战，如稳定性差、靶向特异性弱、难以穿越生理屏障。通过对核酸结构进行化学修饰，可以提高某些核酸药物在体内的稳定性和靶向特异性，从而提高递送效率，降低免疫原性。此外，利用核酸药物载体可以促进药物向病变部位的运输，从而有助于高效的细胞内逃逸并促进体内药物疗效。目前，常用的递送载体包括病毒载体、脂质纳米粒、聚合物纳米粒、无机纳米粒、蛋白载体和细胞外囊泡。然而，单独的修饰或递送载体本身不足以克服许多障碍。核酸化学修饰与药物递送系统的结合有望实现增强的治疗效果。然而，这种方法也增加了技术复杂性和临床转化成本。因此，开发既实用又简单，同时保持高效、低毒和精确的核酸递送的核酸药物载体和核酸化学修饰已成为核酸药物开发领域的一个突出研究重点。本综述全面总结了核酸类药物修饰和递送系统的进展。此外，还讨论了增强核酸药物递送效率的策略，旨在为核酸药物的转化应用提供有价值的见解。
