Chemical control of 2'-hydroxyl-dependent Cas9 target engagement enables CRISPR RNA ribose replacement
Adrian A. Pater, Halle M. Barber, Sruthi Sudhakar, Ramadevi Chilamkurthy, Sunit Kumar Jana, Mansi Parasrampuria, Michael S. Bosmeny, Jacob A Graczyk-Marrs, Seth B. Eddington, Cole A Blazier, Leonora Abdullahu, Elise Malek-Adamian, Christopher L. Barkau, Daniel O’Reilly, Sergey Korolev, , Keith T. Gagnon
This study identifies the role of 2'-hydroxyl groups in crRNA for Cas9 DNA binding and develops chemically stabilized crRNAs with enhanced nuclease resistance and editing efficiency.
bioRxiv · Jan 26, 2026 · PreprintBiochemistry