ArticleJournal of molecular biology2018
Reduction of Nonspecificity Motifs in Synthetic Antibody Libraries.
Article in Journal of molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
42 citing papers in PubMed, 64 citations in OpenAlex.
- Prediction of antibody non-specificity using protein language models and biophysical parameters.mAbs · 2026Article
- Predicting non-specific binding of VHHs using machine learning models with cluster-aware validation.mAbs · 2026Article
- Multi-objective antibody design and optimization using machine learning.Nature reviews bioengineering · 2026Article
- Impact of heme on the therapeutic efficacy of anti-CD20 antibodies.The Journal of biological chemistry · 2026Article
- Computational models for the classification of antibody specificity using heavy chain features.PloS one · 2026Article
- Engineering Single-Chain Antibody Fragment (scFv) Variants Targeting A Disintegrin and Metalloproteinase-17 (ADAM-17).Biomolecules · 2025Article
- Antibody Polyreactivity: A Challenger of Immune Paradigms.Immunology · 2025Review
- Pharmacophore-driven antibody discovery on the yeast surface.bioRxiv : the preprint server for biology · 2025Article
- Determining key residues of engineered scFv antibody variants with improved MMP-9 binding using deep sequencing and machine learning.Computational and structural biotechnology journal · 2024Article
- Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics.Nature reviews. Drug discovery · 2024Review
- Understanding the Specific Implications of Amino Acids in the Antibody Development.The protein journal · 2024Review
- Facile generation of biepitopic antibodies with intrinsic agonism for activating tumor necrosis factor receptors.Cell chemical biology · 2024Article
- Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.Cell chemical biology · 2024Article
- Development of a Human B7-H3-Specific Antibody with Activity against Colorectal Cancer Cells through a Synthetic Nanobody Library.Bioengineering (Basel, Switzerland) · 2024Article
- Article
- i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists.Nature communications · 2024Article
- Facile generation of biepitopic antibodies with intrinsic agonism for activating receptors in the tumor necrosis factor superfamily.bioRxiv : the preprint server for biology · 2023Article
- Biochemical and biophysical characterization of natural polyreactivity in antibodies.Cell reports · 2023Article
- Both intratumoral regulatory T cell depletion and CTLA-4 antagonism are required for maximum efficacy of anti-CTLA-4 antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Surface patches induce nonspecific binding and phase separation of antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Successful antibody development requires both functional binding and desirable biophysical characteristics. In the current study, we analyze the causes of one hurdle to clinical development, off-target reactivity, or nonspecificity. We used a high-throughput nonspecificity assay to isolate panels of nonspecific antibodies from two synthetic single-chain variable fragment libraries expressed on the surface of yeast, identifying both individual amino acids and motifs within the complementarity-determining regions which contribute to the phenotype. We find enrichment of glycine, valine, and arginine as both individual amino acids and as a part of motifs, and additionally enrichment of motifs containing tryptophan. Insertion of any of these motifs into the complementarity-determining region H3 of a "clean" antibody increased its nonspecificity, with greatest increases in antibodies containing Trp or Val motifs. We next applied these rules to the creation of a synthetic diversity library based on natural frameworks with significantly decreased incorporation of such motifs and demonstrated its ability to isolate binders to a wide panel of antigens. This work both provides a greater understanding of the drivers of nonspecificity and provides design rules to increase efficiency in the isolation of antibodies with drug-like properties.
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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.