News

dsRBD Redesign: A Targeted Strategy for Inhibition of RNA Helicase DHX9

We got a new preprint just published. Here, we redesigned double-stranded RNA binding domains to inhibit the RNA helicase DHX9 through a highly specific interface. A proof of principle for inhibitor design based on autoregulatory domains. DHX9 is a highly relevant cancer target as its expression and activity is up-regulated in several cancer types. The targeted interface is essential for DHX9 to be active. The dsRBD2 domain not only recruits dsRNA to the helicase core but is needed in a subsequent step to interact with the core domain to induce conformational changes, allowing the RNA to be threaded through the helicase. As this interface is unique for this particular RNA helicase, a potent inhibitor against it would be a promising inhibitor:
DOI: 10.64898/2026.02.13.705762.