posted on 2021-03-22, 19:35authored byKim Nguyen, Yajun Wang, Whitney E. England, John C. Chaput, Robert C. Spitale
Therapeutic targeting of allele-specific
single nucleotide mutations
in RNA is a major challenge in biology and medicine. Herein, we describe
the utility of the XNAzyme X10-23 to knock down allele-specific mRNA
sequences in cells. We demonstrate the value of this approach by targeting
the “undruggable” mutation G12V in oncogenic KRAS. Our
results demonstrate how catalytic XNAs could be employed to suppress
the expression of mRNAs carrying disease-causing mutations that are
difficult to target at the protein level with small molecule therapeutics.