tiRNA:一种有效、可控的翻译抑制基因沉默技术。

IF 4.9 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
New biotechnology Pub Date : 2025-11-25 Epub Date: 2025-08-06 DOI:10.1016/j.nbt.2025.07.010
Bei Xia, Jiajing Cai, Zhilin He, Qubo Zhu
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引用次数: 0

摘要

近年来,rna靶向治疗在生物医学领域取得了革命性的突破,在调控基因表达方面提供了前所未有的精确度。其中,位阻寡核苷酸(SBOs)代表了一类独特的治疗药物,它通过位阻机制起作用,允许在不降解RNA的情况下产生可逆作用。然而,由于缺乏通用的指导方针,并且需要详细分析mRNA/pre-mRNA特征、关键位点分布和rna结合蛋白相互作用,设计SBOs具有挑战性。为了解决这个问题,我们开发了一种新的基于适配体的技术,称为翻译抑制RNA (tiRNA),它通过将eif4g靶向适配体连接到靶基因5'-UTR的反向互补序列来抑制mRNA翻译。该方法利用mRNA的典型翻译起始机制,采用简单的设计策略特异性靶向和抑制选定mRNA的翻译,而不会影响其他mRNA或导致RNA降解。tiRNA的疗效与siRNA相当,为治疗与蛋白质过表达相关的疾病提供了准确性、安全性和可控性。此外,可以使用特殊设计的中和链逆转tiRNA的作用,恢复正常的mRNA翻译并增强治疗的可控性和个性化。这种方法在癌症、基因治疗和其他需要精确调节蛋白质表达的领域具有重要的应用潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
New biotechnology
New biotechnology 生物-生化研究方法
CiteScore
11.40
自引率
1.90%
发文量
77
审稿时长
1 months
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.
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