Höfer Lab

University of Marburg

Hessen (DE7) · Germany

ERC-funded
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ERC Starting Grant · 2023

Conjugation of NAD-capped RNAs to proteins by ADP-ribosyltransferases to generate RNA therapeutics

Background: We discovered that NAD-capped RNAs can be covalently attached to specific target proteins by the phage T4 ADP-ribosyltransferase (ART) ModB, which we term RNAylation. Scientific problem: RNA therapy has almost limitless yet unexplored potential. Its translation into the clinics, however, requires optimal RNA delivery with high RNA stability, efficient cellular internalisation and precise target affinity. Hypothesis: Protein-RNA interactions are ubiquitous and central in biological control. I hypothesise that conjugating a NAD-capped nucleic acid to a protein catalysed by an ART generates a novel biomolecule – the RNAylated protein – with unique functionalities. The covalently…

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