Definition

A preparation of cell-permeant, short double-stranded DNA fragment that mimics double-strand breaks and linked to a cholesterol molecule, with potential antineoplastic activity. Upon administration of DNA repair inhibiting oligonucleotide, the cholesterol moiety enables tumoral and nuclear uptake of the DNA, and mimics DNA double-strand breaks (DSBs) inside the tumor cells. This triggers false DNA break signals, binding to and activating DNA repair proteins including both poly (ADP-ribose) polymerase (PARP) and DNA-dependent protein kinase (DNA-PK). This prevents the recruitment of these repair proteins at the actual damage site and inhibits various DNA DSB repair pathways including homologous recombination (HR) and non-homologous end joining (NHEJ). This promotes genetic instability and enhances the accumulation of single and double strand DNA breaks, ultimately leading to apoptosis.