Capped or uncapped? Techniques to assess the quality of mRNA molecules

The successful use of mRNA vaccines during the Covid-19 pandemic has created a boom in mRNA therapeutic research and development. The efficacy of mRNA vaccines and therapies relies on the quality of the synthesized molecules – a key feature of which is the 5′-end cap modification. The development of...

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Bibliographic Details
Published in:Current opinion in systems biology 2024-03, Vol.37, p.100503, Article 100503
Main Authors: Tu, Ying, Das, Akashaditya, Redwood-Sawyerr, Chileab, Polizzi, Karen M.
Format: Article
Language:English
Subjects:
5′ capping
Analysis
Biosensors
LC-MS
mRNA
Therapies
Vaccines
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Summary:The successful use of mRNA vaccines during the Covid-19 pandemic has created a boom in mRNA therapeutic research and development. The efficacy of mRNA vaccines and therapies relies on the quality of the synthesized molecules – a key feature of which is the 5′-end cap modification. The development of analytical methods for assessing mRNA quality needs to be prioritized to enable manufacturing development, process control, and rapid assessment of batch quality before release. In this review, we provide an overview of the latest techniques in the analysis of mRNA 5′ capping. We also discuss future possibilities and challenges in quality control of mRNA products at scale. •Interest in RNA therapeutics is on the rise after high-profile successes.•A critical quality attribute of functional mRNA is modification at the 5′ end.•Most existing analytical methods have a tradeoff between information and ease of use.•Key to future manufacturing efforts will be to develop new analytical technology.
ISSN:2452-3100
2452-3100
DOI:10.1016/j.coisb.2023.100503