Allele-Specific RNA Knockdown with a Biologically Stable and Catalytically Efficient XNAzyme

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.

Automated summary

The study demonstrates the utility of XNAzyme X10-23 in targeting allele-specific mRNA sequences in cells, particularly for difficult-to-treat disease-causing mutations. Catalytic XNAs show potential for suppressing mRNA expression carrying disease-causing mutations that are challenging to target at the protein level with conventional small molecule therapeutics.