Targeting telomerase presents several key advantages compared to most other cancer targets in its relative universality, criticality and specificity for cancer cells including cancer stem cells. At present, there are several therapeutic approaches for targeting telomerase in tumors. One in particular, currently undergoing clinical trials, is based on synthetic lipid-modified oligonucleotide antagonists aimed at inhibiting the ribonucleoprotein subunit of human telomerase1 . However, while enabling efficient uptake, the lipid modifications reduce the potency of the therapeutic oligonucleotides compared to non-modified oligonucleotides2 . Non-covalent complexation strategies for cell-penetrating peptide-mediated delivery presents an option to circumvent the need for potency-reducing modifications while allowing for a highly efficient uptake, and could significantly improve the efficiency of telomerase-targeting cancer therapeutics.
The aim of the current work is to assess the capacity for a cell-penetrating peptide designed in our lab, PepFect153 , to efficiently deliver and potentially improve upon the potency of telomerase-inhibiting oligonucleotides.