Therapeutic Gene Silencing of CKAP5 leads to lethality in genetically
unstable cancer cells

Potential of microtubule associated protein targets for cancer therapeutics remains
largely unexplored due to the lack of target specific agents. Herein, we explored the
therapeutic potential of targeting Cytoskeleton Associated Protein 5 (CKAP5), an
important microtubule-associated protein, with CKAP5 targeting siRNAs that are
entrapped in lipid nanoparticles (LNPs). Our screening of 20 solid cancer cell lines
demonstrated selective vulnerability of genetically unstable cancer cell lines in response
to CKAP5 silencing, among which a chemo-resistant ovarian cancer cell line is most
susceptible. In addition, CKAP5 silencing showed significant loss in EB1 dynamics
during mitosis of this chemo resistant ovarian cancer cell line. Finally, we demonstrated
the therapeutic potential in an in-vivo ovarian cancer model, showing increased survival
rate in CKAP5 silenced LNP treated group by 80 % (p<0.0001). Taken together, our
results may ultimately be translated into novel therapeutic modality for Ovarian
Cancer and be utilized for other types of cancers.