{"title":"tiRNA:一种有效、可控的翻译抑制基因沉默技术。","authors":"Bei Xia, Jiajing Cai, Zhilin He, Qubo Zhu","doi":"10.1016/j.nbt.2025.07.010","DOIUrl":null,"url":null,"abstract":"<p><p>RNA-targeted therapies have emerged as a revolutionary breakthrough in biomedicine recently, offering unprecedented precision in regulating gene expression. Among these, steric blocking oligonucleotides (SBOs) represent a unique class of therapeutics that function through a steric blocking mechanism, allowing for reversible effects without RNA degradation. However, designing SBOs is challenging due to the lack of universal guidelines and the need for detailed analysis of mRNA/pre-mRNA characteristics, key site distributions, and RNA-binding protein interactions. To address this, we developed a novel aptamer-based technology called translation inhibition RNA (tiRNA), which inhibits mRNA translation by linking an eIF4G-targeting aptamer to a reverse complementary sequence of the target gene's 5'-UTR. This approach leverages the typical translation initiation mechanism of mRNA and employs a straightforward design strategy to specifically target and inhibit the translation of selected mRNAs without affecting others or causing RNA degradation. The efficacy of tiRNA is comparable to that of siRNA, providing precision, safety, and controllability for treating diseases linked to protein overexpression. Moreover, the effects of tiRNA can be reversed using a specially designed neutralizing strand, restoring normal mRNA translation and enhancing treatment controllability and personalization. This method holds significant potential for applications in cancer, gene therapy, and other fields requiring precise regulation of protein expression.</p>","PeriodicalId":19190,"journal":{"name":"New biotechnology","volume":" ","pages":"177-190"},"PeriodicalIF":4.9000,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"tiRNA: An efficient and controllable gene silencing technology via translation inhibition.\",\"authors\":\"Bei Xia, Jiajing Cai, Zhilin He, Qubo Zhu\",\"doi\":\"10.1016/j.nbt.2025.07.010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>RNA-targeted therapies have emerged as a revolutionary breakthrough in biomedicine recently, offering unprecedented precision in regulating gene expression. Among these, steric blocking oligonucleotides (SBOs) represent a unique class of therapeutics that function through a steric blocking mechanism, allowing for reversible effects without RNA degradation. However, designing SBOs is challenging due to the lack of universal guidelines and the need for detailed analysis of mRNA/pre-mRNA characteristics, key site distributions, and RNA-binding protein interactions. To address this, we developed a novel aptamer-based technology called translation inhibition RNA (tiRNA), which inhibits mRNA translation by linking an eIF4G-targeting aptamer to a reverse complementary sequence of the target gene's 5'-UTR. This approach leverages the typical translation initiation mechanism of mRNA and employs a straightforward design strategy to specifically target and inhibit the translation of selected mRNAs without affecting others or causing RNA degradation. The efficacy of tiRNA is comparable to that of siRNA, providing precision, safety, and controllability for treating diseases linked to protein overexpression. Moreover, the effects of tiRNA can be reversed using a specially designed neutralizing strand, restoring normal mRNA translation and enhancing treatment controllability and personalization. This method holds significant potential for applications in cancer, gene therapy, and other fields requiring precise regulation of protein expression.</p>\",\"PeriodicalId\":19190,\"journal\":{\"name\":\"New biotechnology\",\"volume\":\" \",\"pages\":\"177-190\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2025-11-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"New biotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1016/j.nbt.2025.07.010\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"New biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1016/j.nbt.2025.07.010","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
tiRNA: An efficient and controllable gene silencing technology via translation inhibition.
RNA-targeted therapies have emerged as a revolutionary breakthrough in biomedicine recently, offering unprecedented precision in regulating gene expression. Among these, steric blocking oligonucleotides (SBOs) represent a unique class of therapeutics that function through a steric blocking mechanism, allowing for reversible effects without RNA degradation. However, designing SBOs is challenging due to the lack of universal guidelines and the need for detailed analysis of mRNA/pre-mRNA characteristics, key site distributions, and RNA-binding protein interactions. To address this, we developed a novel aptamer-based technology called translation inhibition RNA (tiRNA), which inhibits mRNA translation by linking an eIF4G-targeting aptamer to a reverse complementary sequence of the target gene's 5'-UTR. This approach leverages the typical translation initiation mechanism of mRNA and employs a straightforward design strategy to specifically target and inhibit the translation of selected mRNAs without affecting others or causing RNA degradation. The efficacy of tiRNA is comparable to that of siRNA, providing precision, safety, and controllability for treating diseases linked to protein overexpression. Moreover, the effects of tiRNA can be reversed using a specially designed neutralizing strand, restoring normal mRNA translation and enhancing treatment controllability and personalization. This method holds significant potential for applications in cancer, gene therapy, and other fields requiring precise regulation of protein expression.
期刊介绍:
New Biotechnology is the official journal of the European Federation of Biotechnology (EFB) and is published bimonthly. It covers both the science of biotechnology and its surrounding political, business and financial milieu. The journal publishes peer-reviewed basic research papers, authoritative reviews, feature articles and opinions in all areas of biotechnology. It reflects the full diversity of current biotechnology science, particularly those advances in research and practice that open opportunities for exploitation of knowledge, commercially or otherwise, together with news, discussion and comment on broader issues of general interest and concern. The outlook is fully international.
The scope of the journal includes the research, industrial and commercial aspects of biotechnology, in areas such as: Healthcare and Pharmaceuticals; Food and Agriculture; Biofuels; Genetic Engineering and Molecular Biology; Genomics and Synthetic Biology; Nanotechnology; Environment and Biodiversity; Biocatalysis; Bioremediation; Process engineering.