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Antibody-oligonucleotide conjugates in cancer therapy: Potential and Promise

Qinghe Meng1, Mo Yang2, Fei Xing3

  • 1Nanomedicine Center, The Great Bay Area National Institute for Nanotechnology Innovation, 136 Kaiyuan Avenue, Guangzhou, Guangdong 510700, China; School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, Guangdong 510006, China.

Critical Reviews in Oncology/Hematology
|July 20, 2025
PubMed

Insights

Antibody-Oligonucleotide Conjugates (AOCs) offer a novel cancer therapy by using gene-modulating oligonucleotides instead of cytotoxic drugs. This approach shifts focus from cell killing to gene regulation for improved targeted treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioconjugation Chemistry

Background:

  • Antibody-Drug Conjugates (ADCs) are advanced oncology therapeutics.
  • ADCs utilize a targeting vehicle, linker, and cytotoxic payload for precise therapy.
  • Antibody-Oligonucleotide Conjugates (AOCs) represent an evolution of ADCs.

Purpose of the Study:

  • To review the biology and chemistry of Antibody-Oligonucleotide Conjugates (AOCs).
  • To examine the design components of AOCs, including antibodies, linkers, and oligonucleotides.
  • To highlight clinical AOC candidates and evaluate challenges and opportunities in cancer treatment.

Main Methods:

  • Literature review of Antibody-Oligonucleotide Conjugates (AOCs).
  • Analysis of AOC design principles: targeting vehicle, linker, and oligonucleotide payload.
  • Evaluation of current clinical AOC candidates for cancer therapy.

Main Results:

  • AOCs replace traditional cytotoxic payloads with gene-modulating oligonucleotides (siRNA, ASO).
  • This shifts therapeutic strategy from cell killing to gene regulation.
  • Several promising AOC candidates are in clinical development for cancer treatment.

Conclusions:

  • AOCs offer a new paradigm in targeted cancer therapy by enabling gene regulation.
  • Advances in AOC design and conjugation chemistry are crucial.
  • AOCs hold significant potential to revolutionize oncology treatment strategies.
Keywords:
Antibody-drug conjugates (ADCs)Antibody-oligonucleotide conjugates (AOCs)Antisense oligonucleotides (ASO)Cancer therapySmall interfering RNA (siRNA)

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