Because of their importance in cell signaling and human disease, integral membrane proteins such as G protein-coupled receptors (GPCRs) and ion channels comprise over 40% of existing drug targets. Monoclonal antibodies (MAbs) that recognize conformation-dependent epitopes on membrane proteins are usually the most valuable type of antibody because they often bind to critical structures of the receptor that can be exploited for its detection or inhibition. However, the development of conformation-dependent, inhibitory MAbs against membrane proteins is especially difficult because, unlike soluble proteins, most membrane proteins are dependent on a lipid environment to maintain their native tertiary and quaternary (oligomeric) structures. Membrane proteins are often difficult to purify, often express at low concentrations on the cell surface, and are usually poorly represented by linear peptides. New approaches are needed to develop such MAbs for therapeutic, diagnostic, and research applications. Here we propose to use a novel technology, the Lipoparticle, to capture and concentrate structurally intact membrane proteins in a format amenable to immunization. The concept of using Lipoparticles to develop antibodies against cellular membrane proteins builds on the historic use of viral particles as successful vaccines.
Public Health Relevance: This proposal will result in monoclonal antibodies against important membrane protein targets for therapeutic development, diagnostics, and biomedical research. Lipoparticles optimized as immunogens will be developed as commercial products.
Thesaurus Terms: Atgn;Abbreviations;Adjuvant;Antibodies;Antigenic Determinants;Antigens;Binding;Binding (Molecular Function);Binding Determinants;Biomedical Research;Blood Serum;Cell Communication And Signaling;Cell Line;Cell Lines, Strains;Cell Signaling;Cell Surface;Cellline;Cells;Cellular Membrane;Dna;Deoxyribonucleic Acid;Detection;Detergents;Development;Diagnostic;Diagnostics Research;Drug Delivery;Drug Delivery Systems;Drug Targeting;Drug Targetings;Environment;Epitopes;G Protein-Complex Receptor;G-Protein-Coupled Receptors;Goals;Hybridomas;Immune;Immune Response;Immunization;Immunoactivators;Immunoadjuvants;Immunologic Adjuvants;Immunologic Stimulation;Immunological Adjuvant;Immunological Stimulation;Immunopotentiators;Immunostimulants;Immunostimulation;Integral Membrane Protein;Intracellular Communication And Signaling;Intrinsic Membrane Protein;Ion Channel;Ionic Channels;Licensing;Lipid Bilayers;Lipids;Mab Therapeutics;Mammals, Mice;Marketing;Membrane;Membrane Channels;Membrane Proteins;Membrane-Associated Proteins;Methods;Mice;Moab, Clinical Treatment;Molecular Configuration;Molecular Conformation;Molecular Interaction;Molecular Stereochemistry;Monoclonal Antibodies;Murine;Mus;Phemx;Phemx Protein;Phemx Protein, Human;Pan-Hematopoietic Expression Protein;Peptides;Preparation;Production;Property;Property, Loinc Axis 2;Proteins;Protocol;Protocols Documentation;Reagent;Receptor Protein;Research;Sensitization, Immunologic;Sensitization, Immunological;Serum;Signal Transduction;Signal Transduction Systems;Signaling;Source;Structure;Surface Proteins;Tssc6;Tssc6 Protein, Human;Testing;Tetraspanin;Therapeutic Monoclonal Antibodies;Timeline;Transmembrane Protein;Tumor-Suppressing Stf 6 Protein;Vaccines;Viral;Viral Vaccines;Virus-Like Particle;Antibody;Biological Signal Transduction;Conformation;Conformational State;Cultured Cell Line;Expression Vector;Gene Product;Host Response;Human Phemx Protein;Human Disease;Immune Adjuvant;Immunogen;Immunoresponse;Improved;Lipid Bilayer Membrane;Membrane Structure;Monoclonal Antibody;New Approaches;New Technology;Novel Approaches;Novel Strategies;Novel Strategy;Pan-Hematopoietic Expression Protein, Human;Particle;Product Development;Receptor;Receptor Function;Success;Therapeutic Development;Tumor Suppressing Subtransferable Candidate 6 Protein, Human;Vaccine Development;Viruslike Particle
