SBIR-STTR Award

Membrane proteins control the flow of information, nutrients, and signals through the cell membrane, and are the targets for more than 40% of FDA-approved drugs. Monoclonal antibodies (MAbs) that target membrane proteins can be exceptionally useful in research, diagnostic, and therapeutic applications, but for most membrane proteins there are no MAbs that recognize the native protein on the cell surface. The need for such MAbs has been recognized by industry and the NIH, but efforts to identify such MAbs are limited by the difficulty in expressing and purifying membrane proteins in exogenous systems and by conventional MAb isolation strategies that typically focus on one target at a time. A novel approach to identify membrane protein MAbs in a high-throughput manner is needed to derive MAbs against the entire human membrane proteome. Here we propose a platform technology that can be used to rapidly isolate MAbs against structurally-intact membrane proteins for therapeutic development, diagnostics, and biomedical research.

Public Health Relevance Statement:


Public Health Relevance:
This proposal will contribute to public health and the cure of human disease by identifying MAbs against native membrane proteins, enabling their development for therapeutics, diagnostics, and biomedical research.

Project Terms:
Abbreviations; Biomedical Research; Cell membrane; Cell surface; Cell Surface Proteins; cell type; Cells; commercial application; Complement; Development; Diagnostic; Diagnostics Research; Epitopes; Exhibits; FDA approved; Goals; Human; Human Cell Line; human disease; Immunization; Industry; Libraries; Membrane; Membrane Proteins; Methods; Molecular; Molecular Conformation; Monoclonal Antibodies; Mutation; novel strategies; Nutrient; Orphan; Performance; Phage Display; Pharmaceutical Preparations; Phase; Plasmids; Protein Array; protein expression; Proteins; Proteome; public health medicine (field); public health relevance; Qualifying; Reagent; Reproducibility; research study; screening; Services; Signal Transduction; Source; Specificity; Staining method; Stains; success; Surface; System; Technology; Testing; Therapeutic; Therapeutic Agents; therapeutic development; Therapeutic Monoclonal Antibodies; Time; Tissues; trafficking; United States National Institutes of Health

Membrane proteins control the flow of information, nutrients, and signals through the cell membrane, and are the targets for 59% of FDA-approved drugs. Monoclonal antibodies (MAbs) that target membrane proteins can be exceptionally valuable in research, diagnostic, and therapeutic applications, but for the vast majority of membrane proteins there are either no MAbs at all or only poor quality antibodies with limited application. The need for high quality MAbs against membrane proteins has been recognized by industry and the NIH, but efforts to identify such MAbs are limited by the difficulty in expressing and purifying membrane proteins in exogenous systems and by conventional MAb isolation strategies that focus on one target at a time. A novel approach to identify membrane protein MAbs in a high-throughput manner is needed to derive MAbs against the entire human membrane proteome. Here we propose a technology that can be used to rapidly isolate high quality MAbs against membrane proteins to fulfill this unmet need.

Public Health Relevance Statement:
PROJECT NARRATIVE This proposal will contribute to public health and the cure of human disease by isolating the largest collection of high quality MAbs against membrane proteins currently available. MAbs that target membrane proteins can be exceptionally valuable in research, diagnostic, and therapeutic applications, but for the vast majority of membrane proteins there are either no MAbs at all or only poor quality antibodies with limited application.

Project Terms:
Affinity; Animals; Antibodies; Bacteriophages; base; Binding; cancer cell; Catalogs; Cell membrane; cell type; Cells; Chickens; Collection; Commercial Catalogs; Development; Diagnostic; Epitopes; experience; FDA approved; Flow Cytometry; Gene Chips; Gold; high standard; Human; human disease; Immunize; immunocytochemistry; Immunofluorescence Immunologic; immunogenicity; Industry; Membrane; Membrane Proteins; Molecular; Molecular Cloning; Monoclonal Antibodies; Neurons; novel strategies; Nutrient; Orphan; Pharmaceutical Preparations; phase 1 study; Plasmids; protein expression; Proteins; Proteome; Protocols documentation; prototype; Public Health; Research; screening; Services; Signal Transduction; Specificity; Stem cells; System; T-Lymphocyte; Technology; Testing; Therapeutic; Time; United States National Institutes of Health; Western Blotting