Protein and Peptide Pharmaceutical Laboratory, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Protein and Peptide Pharmaceutical Laboratory, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
J Control Release. 2014 Nov 10;193:270-81. doi: 10.1016/j.jconrel.2014.04.044. Epub 2014 May 6.
RNA interference (RNAi) was intensively studied in the past decades due to its potential in therapy of diseases. The target specificity and universal treatment spectrum endowed siRNA advantages over traditional small molecules and protein drugs. However, barriers exist in the blood circulation system and the diseased tissues blocked the actualization of RNAi effect, which raised function versatility requirements to siRNA therapeutic agents. Appropriate functionalization of siRNAs is necessary to break through these barriers and target diseased tissues in local or systemic targeted application. In this review, we summarized that barriers exist in the delivery process and popular functionalized technologies for siRNA such as chemical modification and physical encapsulation. Preclinical targeted siRNA delivery and the current status of siRNA based RNAi therapeutic agents in clinical trial were reviewed and finally the future of siRNA delivery was proposed. The valuable experience from the siRNA agent delivery study and the RNAi therapeutic agents in clinical trial paved ways for practical RNAi therapeutics to emerge early.
过去几十年，由于 RNA 干扰 (RNAi) 在疾病治疗方面的潜力，人们对其进行了深入研究。siRNA 比传统小分子和蛋白质药物具有靶向特异性和通用治疗谱的优势。然而，在血液循环系统和病变组织中存在障碍，阻碍了 RNAi 效应的实现，这对 siRNA 治疗剂的功能多样性提出了要求。适当的 siRNA 功能化对于突破这些障碍和在局部或全身靶向应用中靶向病变组织是必要的。在这篇综述中，我们总结了 siRNA 在递药过程中存在的障碍和常用的功能化技术，如化学修饰和物理包裹。综述了靶向 siRNA 的临床前递药和基于 siRNA 的 RNAi 治疗剂的临床现状，并对 siRNA 递药的未来进行了展望。siRNA 递药研究和临床试验中 RNAi 治疗剂的宝贵经验为早期出现实用的 RNAi 治疗铺平了道路。
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