NIH R01 · 2025
Targeted degradation of RNAs by using small molecules
PROJECT SUMMARY We propose a transformative approach, inspired by the mechanism of action of antisense oligonucleotides (ASOs), to cleave RNAs with small molecules in cells and animals. As an alternative to ASOs, we will continue to develop a class of small molecules that selectively cleave an RNA target, with supporting, validating data. Our approach, dubbed ribonuclease targeting chimeras (RiboTACs), engineers small molecules to recruit endogenous RNase L, expressed in a latent (hence RNase L) form. The chimeras, comprising an RNA-binding module and an RNase L-recruiting small molecule, activate RNase L locally at the site of the desired target. Indeed, the goals of our previously funded…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.