RNA editing: Expanding the potential of RNA therapeutics.
RNA editing: Expanding the potential of RNA therapeutics.
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DOI：
10.1016/j.ymthe.2023.01.005
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发表时间：
2023-06-07
期刊：
影响因子：
--
通讯作者：
Mali P
中科院分区：
文献类型：
--
作者：
Booth BJ;Nourreddine S;Katrekar D;Savva Y;Bose D;Long TJ;Huss DJ;Mali P
RNA疗法对医学产生了巨大的影响，最近为抗击COVID-19大流行而快速开发和部署的mRNA疫苗就是例证。此外，已经开发了RNA靶向药物，用于通过选择性mRNA敲低或调节前体mRNA剪接来治疗具有显著未满足的医疗需求的疾病。最近，RNA编辑，特别是反义RNA引导的腺苷脱氨酶作用于基于RNA（阿达尔）的可编程A-to-I编辑，已经成为操纵RNA以能够校正致病突变并调节基因表达和蛋白质功能的有力工具。除了校正致病性突变之外，该技术特别适合于需要瞬时药效学效应的治疗应用，例如治疗急性疼痛、肥胖、病毒感染和炎症，其中不希望将永久性改变引入基因组。此外，蛋白质功能的瞬时调节，例如改变酶的活性位点或蛋白质-蛋白质相互作用的界面，为从再生医学到肿瘤学的治疗途径打开了大门。这些新兴的基于RNA编辑的工具集有望广泛影响生物技术和治疗应用。在这里，我们回顾了治疗性RNA编辑的新兴领域，强调了最近的实验室进展，并讨论了临床开发道路上的关键挑战。基于ADAR的RNA编辑已经成为一种强大的工具，可以改造RNA，纠正致病突变，调节蛋白质功能。我们回顾了治疗性RNA编辑的新兴领域，强调了最近的实验室进展，并讨论了临床开发道路上的关键挑战。
RNA therapeutics have had a tremendous impact on medicine, recently exemplified by the rapid development and deployment of mRNA vaccines to combat the COVID-19 pandemic. In addition, RNA-targeting drugs have been developed for diseases with significant unmet medical needs through selective mRNA knockdown or modulation of pre-mRNA splicing. Recently, RNA editing, particularly antisense RNA-guided adenosine deaminase acting on RNA (ADAR)-based programmable A-to-I editing, has emerged as a powerful tool to manipulate RNA to enable correction of disease-causing mutations and modulate gene expression and protein function. Beyond correcting pathogenic mutations, the technology is particularly well suited for therapeutic applications that require a transient pharmacodynamic effect, such as the treatment of acute pain, obesity, viral infection, and inflammation, where it would be undesirable to introduce permanent alterations to the genome. Furthermore, transient modulation of protein function, such as altering the active sites of enzymes or the interface of protein-protein interactions, opens the door to therapeutic avenues ranging from regenerative medicine to oncology. These emerging RNA-editing-based toolsets are poised to broadly impact biotechnology and therapeutic applications. Here, we review the emerging field of therapeutic RNA editing, highlight recent laboratory advancements, and discuss the key challenges on the path to clinical development. ADAR-based RNA editing has emerged as a powerful tool to engineer RNAs, enable correction of disease-causing mutations, and modulate protein functions. We review the emerging field of therapeutic RNA editing, highlight recent laboratory advancements, and discuss the key challenges on the path to clinical development.
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DOI：
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发表时间：
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期刊：
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影响因子：
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影响因子：
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