Related Experiment Video

Updated: Jul 8, 2026

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
11:02

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction

Published on: September 14, 2018

Antibody-oligonucleotide conjugates: design principles, intracellular delivery, and translational opportunities

Yuqian Li1, Xinlin Liu1,2, Fuyuan Zhang1

  • 1Laboratory of Drug Discovery from Natural Resources and Industrialization, School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, China.

Journal of Hematology & Oncology
|July 6, 2026
PubMed

Insights

Antibody-oligonucleotide conjugates (AOCs) offer targeted gene regulation beyond the liver. Optimizing intracellular delivery and endosomal escape is key for therapeutic success in various diseases.

Area of Science:

  • Biotechnology
  • Therapeutic Drug Development
  • Molecular Medicine

Background:

  • Antibody-oligonucleotide conjugates (AOCs) combine antibody targeting with oligonucleotide gene regulation.
  • AOCs enable targeted delivery, expanding therapeutic potential beyond the liver for intracellular targets.
  • Therapeutic efficacy depends on productive intracellular delivery, not just target binding.

Purpose of the Study:

  • To review key design principles for AOC performance.
  • To discuss the intracellular fate and challenges of AOCs.
  • To highlight translational progress and future directions for AOC therapeutics.

Main Methods:

  • Summarizing design principles: target biology, antibody formats, oligonucleotide payloads, chemical modifications, linkers, and conjugation.
  • Analyzing intracellular trafficking, including receptor-mediated uptake, endosomal escape, and payload release.
  • Reviewing translational progress in neuromuscular disorders, oncology, and CNS diseases.

Main Results:

  • AOC performance is governed by multiple design factors, including antibody and payload characteristics.
  • Endosomal escape is a critical rate-limiting step for AOC biological activity.
  • Significant translational progress is observed in various therapeutic areas.

Conclusions:

  • AOCs represent a promising platform for targeted gene regulation.
  • Overcoming intracellular delivery barriers, particularly endosomal escape, is crucial for next-generation AOCs.
  • Future research should focus on optimizing AOC design for enhanced therapeutic outcomes.
Keywords:
Antibody-oligonucleotide conjugates (AOCs)OligonucleotidesPrecision medicine.Targeted delivery

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