Antibody-oligonucleotide conjugates
An ADC that carries a gene-silencing strand instead of a chemotherapy, so it can switch a protein off rather than poison the cell.
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.
How it works
An internalising antibody delivers a conjugated oligonucleotide into the endosome; a fraction escapes to the cytosol and engages RISC or RNase H.
- Sequence-programmable payload
- Reaches targets with no small-molecule pocket
- Builds on mature ADC conjugation chemistry
- Endosomal escape efficiency is very low
- No oncology clinical candidate reported
- Immunostimulation from oligonucleotide backbones
Latest papers
topQuery for this technology: (TITLE:"Antibody-oligonucleotide conjugates" OR ABSTRACT:"Antibody-oligonucleotide conjugates") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Antibody-oligonucleotide conjugates, not a curated reading list.