# Antibody-oligonucleotide conjugates

Source: https://onco.cc/technologies/antibody-oligonucleotide-conjugates/  
OnCo record `antibody-oligonucleotide-conjugates` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An ADC that carries a gene-silencing strand instead of a chemotherapy, so it can switch a protein off rather than poison the cell.

## Summary

Conjugating siRNA or antisense oligonucleotides to an antibody is the leading attempt to solve delivery of nucleic-acid drugs beyond the liver. Programmes in muscle disease are furthest along; in oncology the approach would allow tumour-selective silencing of undruggable drivers. Endosomal escape, where only a small fraction of internalised payload reaches the cytosol, is the unsolved problem.

## Fields

- Kind: Technology
- Status: preclinical
- Last checked: 2026-09-08
- Tags: frontier; radical
- Principle: An internalising antibody delivers a conjugated oligonucleotide into the endosome; a fraction escapes to the cytosol and engages RISC or RNase H.
- Strengths: Sequence-programmable payload; Reaches targets with no small-molecule pocket; Builds on mature ADC conjugation chemistry
- Limitations: Endosomal escape efficiency is very low; No oncology clinical candidate reported; Immunostimulation from oligonucleotide backbones

## Sources

- ClinicalTrials.gov: antibody oligonucleotide conjugate: https://clinicaltrials.gov/search?term=antibody%20oligonucleotide%20conjugate

## Connected records

- fronts: [Antibody-Drug Conjugates](https://onco.cc/fronts/adcs/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Degrader-antibody conjugate (DAC)](https://onco.cc/technologies/degrader-antibody-conjugate/), [Oligonucleotide therapeutics](https://onco.cc/technologies/antisense-sirna/), [Site-specific conjugation & linker chemistry](https://onco.cc/technologies/site-specific-conjugation/)
- roadmaps: [Radical oncology: what could change the war by 2035](https://onco.cc/roadmaps/frontier-2035/)

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