Date

Thursday 27 Aug 2026

Time

15:15 - 15:45

Location

BW018

Supervisor

Madeline Kavanagh

Jury

Dmitri Filippov

Our understanding of the causes of disease has never been greater, yet the rate of drug development has barely shifted in the past century. Although drug development is primarily focused on targeting proteins, RNA offers an alternative therapeutic target with a potentially increased target space and the possibility of indirectly targeting ‘undruggable’ proteins. There are two main approaches to targeting RNA: oligonucleotides and small molecules. Oligonucleotide-based approaches have achieved the most therapeutic success to date, but they continue to struggle with challenges related to immunogenicity, off-target effects, stability and delivery. Small molecules overcome many of these limitations, but have their own challenges, including poorer affinity and selectivity, and less well-defined design criteria. This colloquium focuses on methods used to identify and validate RNA-targeting small molecules. It discusses DNA-encoded libraries, small molecule microarrays, electrophilic labeling and fragment-based drug discovery as hit identification methods. It also discusses two validation methods that are used to confirm hits: X-ray crystallography and chemical cross-linking and isolation by pull-down. Finally, this colloquium discusses several RNA-targeting small molecules that have entered preclinical or clinical development, which highlights the potential of RNA-targeting small molecules as a promising alternative to targeting proteins.