Grant: Travel Awards - Institute Community Support

Coding Region Determinant-Binding Protein (CRD-BP) is an RNA-binding protein normally only present during early embryo formation where high cell growth is required, but is also found in some tumour cells. CRD-BP provides a protective effect against normal cell RNA degradation mechanisms and can regulate gene expression through interactions with several oncogene messenger RNAs (mRNA) including one called KRAS. KRAS mRNA codes for a protein involved in growth pathways and has heightened activity in some cancers, often harbouring cancer-causing mutations as well as abnormally high levels which necessitates the need for KRAS-targeting drugs. Currently, there are no drugs that target KRAS activity, and attempts thus far have all focussed on KRAS protein. CRD-BP has been discovered to increase KRAS mRNA, the precursor to active protein, which presents a novel opportunity to target KRAS at the RNA level by disrupting the KRAS-CRD-BP interaction. Using biochemical methods, the binding mechanism between CRD-BP and KRAS mRNA is determined, as well as identification of critical parts of CRD-BP that serve as good targets for drug development. Furthermore, preliminary DNA/RNA based molecules are shown here to be capable of disrupting the cancerous interaction in vitro, spearheading an attempt to develop drugs capable of leveraging KRAS-dependent cancers.