Application
A versatile delivery platform for antisense oligonucleotides (ASOs) enabling transient downregulation of protein expression.
Key Benefits
- Broadly boost the efficacy of nucleic acid-based drugs.
- Drastic reduction in toxicity.
- DELVR strategy can rescue clinically tested ASOs that didn’t progress to FDA approval due to off-target effects associated with high dosing.
Market Summary
Antisense oligonucleotides (ASOs) are a class of drugs used to treat genetic and rare diseases, with potential in oncology and personalized medicine. However, their clinical impact is limited by inefficient intracellular delivery. ASOs are typically taken up by cells via endosomes, yet only a small fraction (~0.1%) successfully escape into the cytosol, where they can exert their therapeutic effect. As a result, high doses are required, driving off target effects, immune responses, and significantly increased treatment costs. These limitations highlight the need for improved delivery methods.
Technical Summary
DNA EndosomaL Escape Vehicle Response (DELVR) is a platform designed by researchers at Emory University to dramatically improve the intracellular delivery of ASOs. DELVR integrates four functional components: an ASO, an endosomal escape peptide (EEP), a pH sensitive i‑Motif, and a biocompatible scaffold, to precisely control endosomal release. Following cellular uptake, acidification of the endosome activates the i‑Motif, triggering release of the EEP and enabling rapid endosomal disruption before ASO degradation occurs. This mechanism allows efficient ASO escape into the cytosol, where it can exert its therapeutic effect. Importantly, DELVR is modular: the ASO sequence, escape peptide, and nanoparticle carrier can be readily customized, enabling broad applicability across therapeutic targets and disease indications.
