Dansereau Stephen J, Cui Hua, Dartawan Ricky P, Sheng Jia
Department of Chemistry, The RNA Institute, University at Albany, SUNY, 1400 Washington Ave Extension, Albany, NY 12222, USA.
Genes (Basel). 2025 Jan 2;16(1):48. doi: 10.3390/genes16010048.
The notion of RNA-based therapeutics has gained wide attractions in both academic and commercial institutions. RNA is a polymer of nucleic acids that has been proven to be impressively versatile, dating to its hypothesized RNA World origins, evidenced by its enzymatic roles in facilitating DNA replication, mRNA decay, and protein synthesis. This is underscored through the activities of riboswitches, spliceosomes, ribosomes, and telomerases. Given its broad range of interactions within the cell, RNA can be targeted by a therapeutic or modified as a pharmacologic scaffold for diseases such as nucleotide repeat disorders, infectious diseases, and cancer. RNA therapeutic techniques that have been researched include, but are not limited to, CRISPR/Cas gene editing, anti-sense oligonucleotides (ASOs), siRNA, small molecule treatments, and RNA aptamers. The knowledge gleaned from studying RNA-centric mechanisms will inevitably improve the design of RNA-based therapeutics. Building on this understanding, we explore the physiological diversity of RNA functions, examine specific dysfunctions, such as splicing errors and viral interactions, and discuss their therapeutic implications.
基于RNA的疗法这一概念在学术机构和商业机构中都引起了广泛关注。RNA是一种核酸聚合物，从其假定的RNA世界起源开始，就已被证明具有令人印象深刻的多功能性，在促进DNA复制、mRNA衰变和蛋白质合成的酶促作用中可见一斑。核糖开关、剪接体、核糖体和端粒酶的活性也凸显了这一点。鉴于RNA在细胞内具有广泛的相互作用，它可以成为治疗的靶点，或者被修饰为治疗核苷酸重复紊乱、传染病和癌症等疾病的药物支架。已研究的RNA治疗技术包括但不限于CRISPR/Cas基因编辑、反义寡核苷酸（ASO）、siRNA、小分子治疗和RNA适体。从以RNA为中心的机制研究中获得的知识将不可避免地改进基于RNA的疗法的设计。基于这一理解，我们探讨了RNA功能的生理多样性，研究了特定的功能障碍，如剪接错误和病毒相互作用，并讨论了它们的治疗意义。
