WDR91, an endosomal maturation protein, promotes antisense oligonucleotide activity

Antisense oligonucleotides (ASOs) have emerged as an important class of nucleic acid therapeutics that enable sequence-specific targeting of RNA. Despite substantial advances in ASO chemistry and therapeutic development, efficient intracellular delivery remains a major challenge, as only a small fraction of internalized ASOs escapes endosomal compartments to reach the cytoplasm or nucleus.1 In a recent study published in Molecular Therapy – Nucleic Acids, Menchon and colleagues used a genome-wide CRISPR screen to identify regulators of ASO activity and uncovered the endosomal maturation protein WD repeat domain 91 (WDR91) as a key promoter of ASO activity.