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Chemical Tools for Transcriptome-wide Analysis and Modulation of RNA

Periodic Reporting for period 1 - RiboChem (Chemical Tools for Transcriptome-wide Analysis and Modulation of RNA)

Période du rapport: 2022-05-01 au 2024-10-31

In the RiboChem program we aim to develop new chemical tools that we apply to understand how RNA functions in living organisms.
The chemical tools that we develop are highly specialized and custom made to fit to the needs of our projects. These include tools that can help decipher the structure of RNA,
tools that help elucidate the function of RNA and finally tools that can help us design new drug molecules that can alter the function of RNA.

Our main objectives are threefold:
-Can we identify previously unknown RNAs and elucidate their function?
-Can we decipher what the structure is of RNAs in the cell?
-Can we target RNA with drug molecules?
The RiboChem team has been working towards the goals described above for the last two years.
We have made great progress and finished a suite of highly customized molecules that we are now going to apply to the objectives mentioned.

-We have identified new RNA interactions partners and are currently working on the elucidation of their biological function.
-We have developed chemical crosslinkers that we are applying to decipher RNA 3D structures
-We have made molecules that will be assessed on their potential as RNA targeting drugs.
In an alternative strategy to our current small molecule approach for RNA targeting, we started to explore the use of antisense oligonucleotides as potential antibiotics.
We found that the main problem is the uptake of these large molecules into bacteria. We decided to tackle this problem by developing customized uptake tags that can be appended to the antisense agents.
This approach worked remarkably well and have advanced antisense delivery beyond the state of the art. We are expecting that this will find widespread use in the future.
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