Abstract
RNA repeat expansions cause >30 diseases, and both oligonucleotides and small molecules have been developed to inhibit their dysfunction. Benhamou et al. show for the first time that small molecules targeting structured, disease-causing RNAs can shunt them toward native decay pathways by affecting their processing.
| Original language | American English |
|---|---|
| Pages (from-to) | 223-231.e4 |
| Journal | Cell Chemical Biology |
| Volume | 27 |
| Issue number | 2 |
| DOIs | |
| State | Published - 20 Feb 2020 |
| Externally published | Yes |
Bibliographical note
Funding Information:We dedicate this work to our inspirational colleague Prof. K. Barry Sharpless on the occasion of his award of the Priestly Medal. We thank Jessica Childs-Disney for help writing the manuscript and the agencies that funded this work including the National Institutes of Health (DP1-NS096898 to M.D.D. and F31-NS110269 to A.J.A.), the Muscular Dystrophy Association (grant #380467 to M.D.D.), and a Fullbright Fellowship (to R.I.B.). We also thank the University of Florida's Center for Neurogenetics for the DM2 fibroblast cell line used in this study. M.D.D. directed the study, conceived the ideas, and designed experiments. R.I.B. designed and performed in vitro and cellular experiments and synthesized compounds. A.J.A. and E.T.W. contributed reagents and experimental advice. M.D.D. is a founder of Expansion Therapeutics, and M.D.D. and E.T.W. are scientific consultants for Expansion Therapeutics.
Publisher Copyright:
© 2020 Elsevier Ltd
Keywords
- RNA
- chemical biology
- click chemistry
- drug design
- intron retention
- medicinal chemistry
- microsatellite disease
- myotonic dystrophy
- nucleic acids
- repeat expansion disorder