New method to produce chemically modified mRNA developed
Chemists describes a new synthetically produced, highly modified messenger RNA that allows cells to more efficiently produce proteins
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Previous methods did not allow for the production of mRNAs with chemically modified building blocks at specific positions because mRNAs are produced enzymatically due to their length of several thousands of building blocks. In the new method, the researchers use a so-called ‘expanded genetic alphabet’ during the enzymatic transcription of DNA to RNA. Where normally two base pairs are responsible for transcription, the team introduced a third base pair. This allowed them to introduce unnatural RNA nucleotides into specific mRNA segments, to modify protein production, and to study cellular application in detail.
‘We investigated how stable this chemically modified mRNA is in cells, whether the artificially produced mRNA can be used in cells as a template for efficient protein production, and what influence the chemical modifications have on protein production,’ said Kath-Schorr. The results show that the new method is very powerful for monitoring the introduction of mRNA into cells, and for monitoring and influencing its spread at the cellular level as well as the efficiency of information transcription. This opens up new possibilities to develop efficient mRNA therapies – not only as vaccines, but also in cancer therapy.
In principle, the method could be applied to any mRNA. However, this requires further research, which is currently in planning in cooperation with University Hospital Cologne. In a further step, clinical studies would have to be carried out. Kath-Schorr's team is currently also developing a more efficient method to package mRNAs before introducing them into cells.
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