New method to produce chemically modified mRNA developed

Date:
March 3, 2022
Source:
University of Cologne
Summary:
Chemists describe a new synthetically produced, highly modified
messenger RNA that allows cells to more efficiently produce
proteins. In the long term, this method could open up new
therapeutic options.



FULL STORY ==========================================================================

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In a recent study, the research group at the University of Cologne's
Institute of Organic Chemistry led by Professor Dr Stephanie Kath-Schorr describes a novel method for the enzymatic production of synthetic
messenger RNA (mRNA).

While natural base modifications of mRNA are already being used - for
example by BioNTech/Pfizer for the production of their coronavirus vaccine
- this newly developed mRNA additionally contains site-specifically
introduced, non-natural nucleotides. Nucleotides are molecules that
function as the basic building blocks of RNA. This new approach using non-natural nucleotides allows the scientists to study how mRNA is
introduced into cells and to observe how the newly introduced information spreads at the cellular level. This in turn promises better therapeutic applications in the long run. The article `Stronger together for in cell translation: natural and unnatural base modified mRNA' has appeared in
Chemical Science.

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. In this field, the Institute of Organic Chemistry
is cooperating with other scientists from the Chemistry Department as
well as the Faculty of Medicine within the framework of the UoC Forum `Transformative Nanocarriers for RNA Transport and Tracking - Advanced
Concepts for Therapy and Diagnostic' (iRNA Carriers).

========================================================================== Story Source: Materials provided by University_of_Cologne. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Lisa Bornewasser, Christof Domnick, Stephanie Kath-Schorr. Stronger
together for in cell translation: natural and unnatural base
modified mRNA. Chemical Science, 2022; DOI: 10.1039/D2SC00670G ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220303112212.htm

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