Amplifying gene expression with RNA-targeted therapeutics.
Amplifying gene expression with RNA-targeted therapeutics.
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DOI：
10.1038/s41573-023-00704-7
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发表时间：
2023-07
影响因子：
120.1
通讯作者：
Wahlestedt, Claes
中科院分区：
文献类型：
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作者：
Khorkova, Olga;Stahl, Jack;Joji, Aswathy;Volmar, Claude-Henry;Wahlestedt, Claes
许多疾病是由突变基因的表达不足引起的，并将受益于相应蛋白质的表达增加。然而，在药物开发中，从历史上看，开发具有抑制或拮抗作用的药物更容易。蛋白质替代和基因治疗可以达到增加蛋白质表达的目的，但存在局限性。最近发现的由非编码RNA形成的广泛的调控网络为放大特定蛋白质的生产提供了替代的目标和策略。除了以RNA为靶点的小分子外，基于核酸的新治疗方式正在开发中，这种治疗方式允许对基于RNA的调控网络进行高度特异性的调节。这些方法可以直接针对mRNAs的稳定性或调节非编码RNA介导的转录和翻译调节。这篇综述重点介绍了新出现的针对RNA的基因激活治疗方法，重点介绍了转化为临床的机会和挑战。许多疾病涉及特定蛋白质水平的降低或缺失，并将受益于提高基因表达的治疗。在他们的评论中，霍尔科娃等人。讨论正在开发的旨在促进基因表达的RNA靶向疗法的日益广泛的范围，包括针对非编码RNA物种的复杂调控网络的核酸疗法。
Many diseases are caused by insufficient expression of mutated genes and would benefit from increased expression of the corresponding protein. However, in drug development, it has been historically easier to develop drugs with inhibitory or antagonistic effects. Protein replacement and gene therapy can achieve the goal of increased protein expression but have limitations. Recent discoveries of the extensive regulatory networks formed by non-coding RNAs offer alternative targets and strategies to amplify the production of a specific protein. In addition to RNA-targeting small molecules, new nucleic acid-based therapeutic modalities that allow highly specific modulation of RNA-based regulatory networks are being developed. Such approaches can directly target the stability of mRNAs or modulate non-coding RNA-mediated regulation of transcription and translation. This Review highlights emerging RNA-targeted therapeutics for gene activation, focusing on opportunities and challenges for translation to the clinic. Many diseases involve reduced or absent levels of a particular protein and would benefit from therapies that increase gene expression. In their Review, Khorkova et al. discuss the growing range of RNA-targeted therapies in development that aim to boost gene expression, including nucleic acid-based therapeutics targeting the complex regulatory network of non-coding RNA species.
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影响因子：
16.6
作者：
通讯作者：
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影响因子：
3.9
作者：
Wang Y;Mao Y;Zhao Y;Yi X;Ding G;Yu C;Sheng J;Liu X;Meng Y;Huang H
通讯作者：
Huang H
影响因子：
5.4
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影响因子：
7.3
作者：
Costales, Matthew G.;Childs-Disney, Jessica L.;Disney, Matthew D.
通讯作者：
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用小分子靶向 RNA 结构。
DOI：
10.1038/s41573-022-00521-4
发表时间：
2022-10
期刊：
Nature reviews. Drug discovery
影响因子：
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作者：
通讯作者：
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