State Key Laboratory of Analytical Chemistry for Life Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
Molecules. 2022 Oct 9;27(19):6717. doi: 10.3390/molecules27196717.
With the increasing understanding of various disease-related noncoding RNAs, ncRNAs are emerging as novel drugs and drug targets. Nucleic acid drugs based on different types of noncoding RNAs have been designed and tested. Chemical modification has been applied to noncoding RNAs such as siRNA or miRNA to increase the resistance to degradation with minimum influence on their biological function. Chemical biological methods have also been developed to regulate relevant noncoding RNAs in the occurrence of various diseases. New strategies such as designing ribonuclease targeting chimeras to degrade endogenous noncoding RNAs are emerging as promising approaches to regulate gene expressions, serving as next-generation drugs. This review summarized the current state of noncoding RNA-based theranostics, major chemical modifications of noncoding RNAs to develop nucleic acid drugs, conjugation of RNA with different functional biomolecules as well as design and screening of potential molecules to regulate the expression or activity of endogenous noncoding RNAs for drug development. Finally, strategies of improving the delivery of noncoding RNAs are discussed.
随着对各种疾病相关非编码 RNA 的认识不断增加，非编码 RNA 作为新型药物和药物靶点逐渐兴起。已经设计并测试了基于不同类型非编码 RNA 的核酸药物。已经对 siRNA 或 miRNA 等非编码 RNA 进行了化学修饰，以增加对降解的抗性，同时对其生物学功能的影响最小。还开发了化学生物学方法来调节各种疾病发生过程中的相关非编码 RNA。新的策略，如设计靶向嵌合体的核糖核酸酶来降解内源性非编码 RNA，作为调节基因表达的有前途的方法，正在成为下一代药物。本文综述了基于非编码 RNA 的治疗学的现状、开发核酸药物的非编码 RNA 的主要化学修饰、不同功能生物分子与 RNA 的缀合以及设计和筛选潜在分子以调节内源性非编码 RNA 的表达或活性用于药物开发。最后，讨论了提高非编码 RNA 递送的策略。
