Antisense oligonucleotide activity in tumour cells is influenced by intracellular LBPA distribution and extracellular vesicle recycling

Abstract

Kapustin et al. investigate the intracellular trafficking of anti-KRAS antisense oligonucleotides. They show that the oligonucleotide AZD4785 is recycled via late endosomes in extracellular vesicles in both cells with poor and good oligo productive uptake, and that inducing lysobisphosphatidic acid in late endosomes or blocking EV recycling enhance AZD4785 activity in cells with poor productive uptake, potentially offering improved treatment strategies.