Using small molecules to modulate RNA stability is an emerging paradigm which holds promise to greatly expand the space of druggable biomolecules. In this talk I will present two divergent applications of small molecule-induced targeted RNA degradation. Firstly, we devised a click chemistry- and degradation-based method to map RNA modifications, meCLICK-Seq. This unorthodox approach enabled discovery of widespread methylation in low-abundance RNA species, greatly expanding the map of the known methylome. In the second application, we harnessed the degradation strategy to develop small molecules which bind and degrade targeted RNAs. We thus rationally designed anti-SARS-CoV-2 agents which compromise its genomic RNA, exerting an anti-viral effect in cellular and mouse models of SARS-CoV-2 infection. Altogether, these novel RNA manipulation methods enable new, diverse applications, both for basic research and development of therapeutics.

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Speaker(s)

Sigitas MIKUTIS

Postdoctoral fellow, Yusuf Hamied Department of Chemistry, University of Cambridge, UK