ArticleNucleic acids research2017
A cell-penetrating antibody inhibits human RAD51 via direct binding.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed.
- Cell-penetrating antibody enhances nuclear delivery of triplex-forming oligonucleotides targeting HER2-positive cancers.Molecular therapy. Nucleic acids · 2025Article
- Harnessing ExDNA for precision exatecan delivery in cancer: a novel antibody-drug conjugate approach.Molecular cancer · 2025Article
- Systemic administration of an RNA binding and cell-penetrating antibody targets therapeutic RNA to multiple mouse models of cancer.Science translational medicine · 2025Article
- Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition.Oncotarget · 2024Article
- Toxic PARP trapping upon cAMP-induced DNA damage reinstates the efficacy of endocrine therapy and CDK4/6 inhibitors in treatment-refractory ER+ breast cancer.Nature communications · 2023Article
- Selective Inhibition of ATM-dependent Double-strand Break Repair and Checkpoint Control Synergistically Enhances the Efficacy of ATR Inhibitors.Molecular cancer therapeutics · 2023Article
- Roles of homologous recombination in response to ionizing radiation-induced DNA damage.International journal of radiation biology · 2023Review
- The role of cell-penetrating peptides in potential anti-cancer therapy.Clinical and translational medicine · 2022Review
- Article
- Targeting RAD51-Mediated Homologous Recombination as a Treatment for Advanced Solid and Hematologic Malignancies: Opportunities and Challenges Ahead.OncoTargets and therapy · 2022Review
- ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody.JCI insight · 2021Article
- A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death.Cell chemical biology · 2021Article
- Cell-Penetrating Peptides: Applications in Tumor Diagnosis and Therapeutics.Pharmaceutics · 2021Review
- Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer.Cancer cell international · 2021Article
- Exploiting DNA repair pathways for tumor sensitization, mitigation of resistance, and normal tissue protection in radiotherapy.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Antibody-Mediated Enzyme Therapeutics and Applications in Glycogen Storage Diseases.Trends in molecular medicine · 2019Review
- A Novel Cell-Penetrating Antibody Fragment Inhibits the DNA Repair Protein RAD51.Scientific reports · 2019Article
- Synthetic lethality of a cell-penetrating anti-RAD51 antibody in PTEN-deficient melanoma and glioma cells.Oncotarget · 2019Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
RAD51, a key factor in homology-directed repair (HDR), has long been considered an attractive target for cancer therapy, but few specific inhibitors have been found. A cell-penetrating, anti-DNA, lupus autoantibody, 3E10, was previously shown to inhibit HDR, sensitize tumors to radiation, and mediate synthetic lethal killing of BRCA2-deficient cancer cells, effects that were initially attributed to its affinity for DNA. However, as the molecular basis for its ability to inhibit DNA repair, we report that 3E10 directly binds to the N-terminus of RAD51, sequesters RAD51 in the cytoplasm, and impedes RAD51 binding to DNA. Further, we generate separation-of-function mutations in the complementarity-determining regions of 3E10 revealing that inhibition of HDR tracks with binding to RAD51 but not to DNA, whereas cell penetration is linked to DNA binding. The consequences of these mutations on putative 3E10 interactions with RAD51 and DNA are correlated with in silico molecular modeling. Taken together, the results identify 3E10 as a novel inhibitor of RAD51 by direct binding, accounting for its ability to suppress HDR and providing the molecular basis to guide pre-clinical development of 3E10 as an anti-cancer agent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.