Particle.news

Download on the App Store

AP1M1 Knockout Validated to Enhance Antisense Drug Delivery, Guiding Broader RNA Therapy Development

Disruption of AP1M1 extends endosomal retention of antisense drugs, with ongoing tests of its application to broader RNA therapies alongside pathogen interventions.

Image

Overview

  • A genome-wide CRISPR/Cas9 screen identified AP1M1 and other trafficking genes that regulate endosome-to-lysosome transport of antisense oligonucleotides (ASOs).
  • Knockout of AP1M1 in cell cultures and mouse models prolonged ASO residence in endosomes and significantly boosted target RNA suppression without increasing dosage.
  • This strategy addresses a key delivery barrier that limits the efficacy of ASO treatments for disorders such as ALS and Duchenne muscular dystrophy.
  • Following in vitro and in vivo validation, researchers are extending the approach to optimize delivery for a wider array of RNA-based therapeutics.
  • Investigators are evaluating whether modulating endosomal transport can also hinder bacterial and viral escape, pointing to potential anti-pathogen applications.