ArticleJournal of computational chemistry2013
Structure-based redesign of proteins for minimal T-cell epitope content.
Article in Journal of computational chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed.
- Preclinical evaluation of high-dose Griffithsin carrageenan fast-dissolving insert for HIV, HSV-2, and HPV prevention.Microbiology spectrum · 2026Article
- Tuning ProteinMPNN to reduce protein visibility via MHC Class I through direct preference optimization.Protein engineering, design & selection : PEDS · 2025Article
- Assessing the predictive ability of computational epitope prediction methods on Fel d 1 and other allergens.PloS one · 2024Article
- Resistor: An algorithm for predicting resistance mutations via Pareto optimization over multistate protein design and mutational signatures.Cell systems · 2022Article
- MHCEpitopeEnergy, a Flexible Rosetta-Based Biotherapeutic Deimmunization Platform.Journal of chemical information and modeling · 2021Article
- Deimmunization of protein therapeutics - Recent advances in experimental and computational epitope prediction and deletion.Computational and structural biotechnology journal · 2021Review
- Computationally optimized deimmunization libraries yield highly mutated enzymes with low immunogenicity and enhanced activity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- EpiSweep: Computationally Driven Reengineering of Therapeutic Proteins to Reduce Immunogenicity While Maintaining Function.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Design and engineering of deimmunized biotherapeutics.Current opinion in structural biology · 2016Review
- Protein deimmunization via structure-based design enables efficient epitope deletion at high mutational loads.Biotechnology and bioengineering · 2015Article
- Depletion of T cell epitopes in lysostaphin mitigates anti-drug antibody response and enhances antibacterial efficacy in vivo.Chemistry & biology · 2015Article
- Mapping the Pareto optimal design space for a functionally deimmunized biotherapeutic candidate.PLoS computational biology · 2015Article
- HIV-1 and its resistance to peptidic carbohydrate-binding agents (CBAs): an overview.Molecules (Basel, Switzerland) · 2014Review
- Computationally driven deletion of broadly distributed T cell epitopes in a biotherapeutic candidate.Cellular and molecular life sciences : CMLS · 2014Article
- Removing T-cell epitopes with computational protein design.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- A high throughput MHC II binding assay for quantitative analysis of peptide epitopes.Journal of visualized experiments : JoVE · 2014Article
- Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
The protein universe displays a wealth of therapeutically relevant activities, but T-cell driven immune responses to non-"self" biological agents present a major impediment to harnessing the full diversity of these molecular functions. Mutagenic T-cell epitope deletion seeks to mitigate the immune response, but can typically address only a small number of epitopes. Here, we pursue a "bottom-up" approach that redesigns an entire protein to remain native-like but contain few if any immunogenic epitopes. We do so by extending the Rosetta flexible-backbone protein design software with an epitope scoring mechanism and appropriate constraints. The method is benchmarked with a diverse panel of proteins and applied to three targets of therapeutic interest. We show that the deimmunized designs indeed have minimal predicted epitope content and are native-like in terms of various quality measures, and moreover that they display levels of native sequence recovery comparable to those of non-deimmunized designs.
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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.