George Kumar: Targeting the Untargetable
George Kumar, Senior Director. Medical Diagnostics Pan Tumor & GI Cancers at AstraZeneca, shared on LinkedIn about a recent paper by Yogitha S Chareddy et al. published on JCI:
“Targeting the Untargetable: A Dual RNAi Breakthrough in KRAS-Driven Cancers
New molecular technology targets tumors and simultaneously silences two ‘undruggable’ cancer genes
A groundbreaking study just published in JCI (July 2025) presents a novel RNAi-based therapeutic strategy that co-targets KRAS and MYC—two oncogenes long considered ‘undruggable’ – using a single inverted chimeric siRNA molecule.
- Dual gene silencing with one molecule
- 10–40× more potent than conventional siRNAs
- EGFR-targeted delivery enables precise tumor uptake
- In vivo models show ~132% tumor growth inhibition when combined with sotorasib (KRAS^G12C^ inhibitor)
This next-generation RNAi design could open new doors for targeting resistant KRAS-driven cancers and redefining the landscape of precision oncology.”
Title: Inverted chimeric RNAi molecules synergistically co-target MYC and KRAS in KRAS-driven cancers
Authors: Yogitha S Chareddy,1 Hayden P. Huggins, Snehasudha S Sahoo, Lyla Stanland, Christina Gutierrez-Ford, Kristina M. Whately, Lincy Edatt,3 Salma H Azam,1 Matthew C. Fleming, Jonah Im, Alessandro Porrello, Imani Simmons, Jillian L. Perry, Albert A. Bowers, Martin Egli, and Chad V. Pecot
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