ArticleScience advances2021
Rational antibody design for undruggable targets using kinetically controlled biomolecular probes.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Identification ofJournal of proteome research · 2025Article
- Dry resist lamination for wafer-scale fabrication of microfluidic superfusion devices.Scientific reports · 2025Article
- Novel druggable space in human KRAS G13D discovered using structural bioinformatics and a P-loop targeting monoclonal antibody.Scientific reports · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Antibody-Loading of Biological Nanocarrier Vesicles Derived from Red-Blood-Cell Membranes.ACS omega · 2024Article
- Recent Progress in Antibody Epitope Prediction.Antibodies (Basel, Switzerland) · 2023Review
- Progress Identifying and Analyzing the Human Proteome: 2021 Metrics from the HUPO Human Proteome Project.Journal of proteome research · 2021Article
- Targeting the Transcriptome Through Globally Acting Components.Frontiers in genetics · 2021Review
Corrections and comments
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several important drug targets, e.g., ion channels and G protein-coupled receptors, are extremely difficult to approach with current antibody technologies. To address these targets classes, we explored kinetically controlled proteases as structural dynamics-sensitive druggability probes in native-state and disease-relevant proteins. By using low-Reynolds number flows, such that a single or a few protease incisions are made, we could identify antibody binding sites (epitopes) that were translated into short-sequence antigens for antibody production. We obtained molecular-level information of the epitope-paratope region and could produce high-affinity antibodies with programmed pharmacological function against difficult-to-drug targets. We demonstrate the first stimulus-selective monoclonal antibodies targeting the transient receptor potential vanilloid 1 (TRPV1) channel, a clinically validated pain target widely considered undruggable with antibodies, and apoptosis-inducing antibodies selectively mediating cytotoxicity in KRAS-mutated cells. It is our hope that this platform will widen the scope of antibody therapeutics for the benefit of patients.
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Registered trials
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