ArticleThe EMBO journal2003
Intrabodies based on intracellular capture frameworks that bind the RAS protein with high affinity and impair oncogenic transformation.
Article in The EMBO journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Tumor-specific cytosol-penetrating antibodies for antigen- and TME-dependent intracellular cargo delivery.Molecular therapy. Oncology · 2025Article
- A Conditionally Activated Cytosol-Penetrating Antibody for TME-Dependent Intracellular Cargo Delivery.Antibodies (Basel, Switzerland) · 2024Article
- Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications.BME frontiers · 2024Review
- The acidic stretch and the C-terminal nuclear export signal motif of NPM1 mutant: are they druggable in AML?Leukemia · 2023Review
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Evolution of nanobodies specific for BCL11A.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Evaluation of variable new antigen receptors (vNARs) as a novel cathepsin S (CTSS) targeting strategy.Frontiers in pharmacology · 2023Article
- Recent advancements in targeted protein knockdown technologies-emerging paradigms for targeted therapy.Exploration of targeted anti-tumor therapy · 2023Review
- Engineering an autonomous VH domain to modulate intracellular pathways and to interrogate the eIF4F complex.Nature communications · 2022Article
- Therapeutic Potential of Intrabodies for Cancer Immunotherapy: Current Status and Future Directions.Antibodies (Basel, Switzerland) · 2022Review
- Antibody-Based Approaches to Target Pancreatic Tumours.Antibodies (Basel, Switzerland) · 2022Review
- Targeting the "undruggable" RAS with biologics.Advances in cancer research · 2022Review
- Single-domain antibody screening byLife science alliance · 2022Article
- Disulfide-compatible phage-assisted continuous evolution in the periplasmic space.Nature communications · 2021Article
- RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site.Nature communications · 2021Article
- A cell-based screening method using an intracellular antibody for discovering small molecules targeting the translocation protein LMO2.Science advances · 2021Article
- If Virchow and Ehrlich Had Dreamt Together: What the Future Holds forInternational journal of molecular sciences · 2021Review
- In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells.Nature communications · 2020Article
- Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020Review
- A potent KRAS macromolecule degrader specifically targeting tumours with mutant KRAS.Nature communications · 2020Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have applied in vivo intracellular antibody capture (IAC) technology to isolate human intrabodies which bind to the oncogenic RAS protein. IAC facilitates the capture of antibody fragments, in this case single-chain Fvs (scFvs), which tolerate reducing environments, such as the cytoplasm of cancer cells. Three anti-RAS scFvs with different affinity, solubility and intracellular binding activity were characterized. The anti-RAS scFvs with highest affinity were expressed relatively poorly in mammalian cells, and greater soluble expression was achieved by mutating the antibody framework to canonical consensus scaffolds, previously derived from IAC, without losing antigen specificity. Mutagenesis experiments showed that the consensus scaffolds are functional as intrabody fragments without an intra-domain disulfide bond. Furthermore, we could convert an intrabody which does not bind RAS in mammalian cells into a high-affinity reagent capable of inhibiting RAS-mediated NIH 3T3 transformation by exchanging VH and VL complementarity-determining regions onto its consensus scaffold. These data show that the consensus scaffold is a robust framework by which to improve intrabody function.
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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.