Characterization of mRNA therapeutics

IF 6.9 2区 化学 Q1 SPECTROSCOPY Mass Spectrometry Reviews Pub Date : 2023-07-04 DOI:10.1002/mas.21856
Guilherme J. Guimaraes, Jaeah Kim, Michael G. Bartlett
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Abstract

Therapeutic messenger RNAs (mRNAs) have emerged as powerful tools in the treatment of complex diseases, especially for conditions that lack efficacious treatment. The successful application of this modality can be attributed to its ability to encode entire proteins. While the large nature of these molecules has supported their success as therapeutics, its extended size creates several analytical challenges. To further support therapeutic mRNA development and its deployment in clinical trials, appropriate methods to support their characterization must be developed. In this review, we describe current analytical methods that have been used in the characterization of RNA quality, identity, and integrity. Advantages and limitations from several analytical techniques ranging from gel electrophoresis to liquid chromatography–mass spectrometry and from shotgun sequencing to intact mass measurements are discussed. We comprehensively describe the application of analytical methods in the measurements of capping efficiency, poly A tail analysis, as well as their applicability in stability studies.

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mRNA 疗法的特征。
治疗性信使核糖核酸(mRNA)已成为治疗复杂疾病的有力工具,尤其是对于缺乏有效治疗手段的疾病。这种模式的成功应用可归功于其编码整个蛋白质的能力。虽然这些分子的巨大特性支持了它们作为治疗药物的成功,但其扩展的尺寸也带来了一些分析上的挑战。为了进一步支持治疗用 mRNA 的开发及其在临床试验中的应用,必须开发出支持其表征的适当方法。在本综述中,我们将介绍目前用于表征 RNA 质量、特性和完整性的分析方法。我们讨论了从凝胶电泳到液相色谱-质谱法,从枪式测序到完整质量测量等几种分析技术的优势和局限性。我们全面介绍了分析方法在封盖效率测量、聚 A 尾分析中的应用,以及它们在稳定性研究中的适用性。
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来源期刊
Mass Spectrometry Reviews
Mass Spectrometry Reviews 物理-光谱学
CiteScore
16.30
自引率
3.00%
发文量
56
期刊介绍: The aim of the journal Mass Spectrometry Reviews is to publish well-written reviews in selected topics in the various sub-fields of mass spectrometry as a means to summarize the research that has been performed in that area, to focus attention of other researchers, to critically review the published material, and to stimulate further research in that area. The scope of the published reviews include, but are not limited to topics, such as theoretical treatments, instrumental design, ionization methods, analyzers, detectors, application to the qualitative and quantitative analysis of various compounds or elements, basic ion chemistry and structure studies, ion energetic studies, and studies on biomolecules, polymers, etc.
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