RNAa: Mechanisms, therapeutic potential, and clinical progress.

IF 6.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Molecular Therapy. Nucleic Acids Pub Date : 2025-02-21 eCollection Date: 2025-06-10 DOI:10.1016/j.omtn.2025.102494

Yukang Qian, Cody Liu, Xuhui Zeng, Long-Cheng Li

{"title":"RNAa: Mechanisms, therapeutic potential, and clinical progress.","authors":"Yukang Qian, Cody Liu, Xuhui Zeng, Long-Cheng Li","doi":"10.1016/j.omtn.2025.102494","DOIUrl":null,"url":null,"abstract":"<p><p>RNA activation (RNAa), a gene regulatory mechanism mediated by small activating RNAs (saRNAs) and microRNAs (miRNAs), has significant implications for therapeutic applications. Unlike small interfering RNA (siRNA), which is known for gene silencing in RNA interference (RNAi), synthetic saRNAs can stably upregulate target gene expression at the transcriptional level through the assembly of the RNA-induced transcriptional activation (RITA) complex. Moreover, the dual functionality of endogenous miRNAs in RNAa (hereafter referred to as mi-RNAa) reveals their complex role in cellular processes and disease pathology. Emerging studies suggest saRNAs' potential as a novel therapeutic modality for diseases such as metabolic disorders, hearing loss, tumors, and Alzheimer's. Notably, MTL-CEBPA, the first saRNA drug candidate, shows promise in hepatocellular carcinoma treatment, while RAG-01 is being explored for non-muscle-invasive bladder cancer, highlighting clinical advancements in RNAa. This review synthesizes our current understanding of the mechanisms of RNAa and highlights recent advancements in the study of mi-RNAa and the therapeutic development of saRNAs.</p>","PeriodicalId":18821,"journal":{"name":"Molecular Therapy. Nucleic Acids","volume":"36 2","pages":"102494"},"PeriodicalIF":6.1000,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930103/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy. Nucleic Acids","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.omtn.2025.102494","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/10 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

RNA activation (RNAa), a gene regulatory mechanism mediated by small activating RNAs (saRNAs) and microRNAs (miRNAs), has significant implications for therapeutic applications. Unlike small interfering RNA (siRNA), which is known for gene silencing in RNA interference (RNAi), synthetic saRNAs can stably upregulate target gene expression at the transcriptional level through the assembly of the RNA-induced transcriptional activation (RITA) complex. Moreover, the dual functionality of endogenous miRNAs in RNAa (hereafter referred to as mi-RNAa) reveals their complex role in cellular processes and disease pathology. Emerging studies suggest saRNAs' potential as a novel therapeutic modality for diseases such as metabolic disorders, hearing loss, tumors, and Alzheimer's. Notably, MTL-CEBPA, the first saRNA drug candidate, shows promise in hepatocellular carcinoma treatment, while RAG-01 is being explored for non-muscle-invasive bladder cancer, highlighting clinical advancements in RNAa. This review synthesizes our current understanding of the mechanisms of RNAa and highlights recent advancements in the study of mi-RNAa and the therapeutic development of saRNAs.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

RNAa：机制、治疗潜力和临床进展。

RNA 激活（RNAa）是一种由小激活 RNA（saRNA）和微 RNA（miRNA）介导的基因调控机制，对治疗应用具有重要意义。与在 RNA 干扰（RNAi）中用于基因沉默的小干扰 RNA（siRNA）不同，合成 saRNA 可通过组装 RNA 诱导的转录激活（RITA）复合物，在转录水平上稳定上调目标基因的表达。此外，内源性 miRNA 在 RNAa（以下简称 mi-RNAa）中的双重功能揭示了它们在细胞过程和疾病病理中的复杂作用。新近的研究表明，saRNAs 有可能成为治疗代谢紊乱、听力损失、肿瘤和阿尔茨海默氏症等疾病的新型疗法。值得注意的是，首个 saRNA 候选药物 MTL-CEBPA 显示出治疗肝细胞癌的前景，而 RAG-01 正在探索用于治疗非肌层浸润性膀胱癌，这突显了 RNAa 的临床进展。本综述综述了我们目前对 RNAa 机制的理解，并重点介绍了 mi-RNAa 研究和 saRNAs 治疗开发方面的最新进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Molecular Therapy. Nucleic Acids MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

15.40

自引率

1.10%

发文量

336

审稿时长

20 weeks

期刊介绍： Molecular Therapy Nucleic Acids is an international, open-access journal that publishes high-quality research in nucleic-acid-based therapeutics to treat and correct genetic and acquired diseases. It is the official journal of the American Society of Gene & Cell Therapy and is built upon the success of Molecular Therapy. The journal focuses on gene- and oligonucleotide-based therapies and publishes peer-reviewed research, reviews, and commentaries. Its impact factor for 2022 is 8.8. The subject areas covered include the development of therapeutics based on nucleic acids and their derivatives, vector development for RNA-based therapeutics delivery, utilization of gene-modifying agents like Zn finger nucleases and triplex-forming oligonucleotides, pre-clinical target validation, safety and efficacy studies, and clinical trials.