Integral Molecular is a research-driven biotechnology company enabling antibody discovery against complex membrane proteins. The company provides characterization services, reagents, and a full antibody discovery platform optimized to work with membrane protein targets, including GPCRs, ion channels, and transporters.
Founded in 2001, Integral has worked with over 300 different partners and customers, including all top 10 pharmaceutical companies.
Integral Molecular offers pseudotyped Reporter Virus Particles to test infectivity and neutralization for:
• SARS-CoV-2 D614G
• Dengue serotypes 1-4
Reporter Virus Particles (RVPs) are replication-incompetent pseudotyped virus particles that enable safe (BSL-2), easy, and high-throughput viral infectivity and neutralization assays using standard detection instrumentation. RVPs display antigenically correct envelope/spike protein and carry a modified genome that expresses a convenient
optical reporter gene (GFP or luciferase) within 24 hours of cellular infection. RVPs are available as a ready-to-use reagent that provides a safe and efficient alternative to plaque assays, and are produced under quality-controlled conditions as a critical reagent to enable regulatory submissions.
Applications of RVPs
• Antibody neutralization
• Serum screening
• High-throughput assays
Advantages of SARS-CoV-2 RVPs
• Safe in a BSL-2 environment
• Quantitative (luciferase) or fluorescent (GFP) read-out
• Compatible with high-throughput plate-based assays
• Quality-controlled production for use as a critical reagent
Click here for additional information on coronavirus RVPS
Click here for additional information on dengue and Zika RVPs
• Whitbeck ET AL. 2020. Antigenicity, Stability and Reproducibility of Zika Reporter Virus Particles for Long-term Applications. PLoS Negl Trop Dis. 14(11):e0008730. doi: 10.1371/journal.pntd.0008730
• Mattia ET AL. 2011. Dengue Reporter Virus Particles for Measuring Neutralizing Antibodies Against Each of the Four Dengue Serotypes. PLOS ONE 6(11):e27252. doi: 10.1371/journal.pone.0027252.
Approximately 25% of antibodies are polyspecific and off-target drug binding can lead to serious adverse events. De-risk your program by choosing the right lead molecule using Integral Molecular’s Membrane Proteome Array. MPA is the largest array of membrane proteins for specificity profiling of biotherapeutics including antibodies and CAR-T cell therapy.
Advantages of the Membrane Proteome Array:
• 6,000 human membrane proteins (~95% of the membrane proteome)
• Sensitive detection of physiologically relevant targets using high throughput flow cytometry
• Screening on live, unfixed cells preserves native epitopes
• Fully validated, IND-ready interaction report in 4 weeks
Applications of the Membrane Proteome Array:
• Specificity Profiling: Your antibody or CAR-T therapeutic is screened to identify potential off-target interactions
• Antibody Deorphaning: Your antibody is screened to identify binding partner(s)
Membrane Proteome Array Case Studies
• Click here to see how FairJourney established that their antibodies do not demonstrate off-target binding
• Click here to understand how a MAb can cross-react with a completely unrelated protein
• Click here to learn how the Membrane Proteome Array was used to deorphan panels of antibodies with unknown targets
Integral Molecular’s proprietary Shotgun Mutagenesis technology is used to reliably map conformational epitopes at single amino acid resolution with a >95% success rate. We have mapped 1,000+ epitopes to date, including:
• Epitopes on GPCRs, transporters, and viral envelope proteins
• Conformational epitopes
• Epitopes on multi-subunit proteins
• State-dependent epitopes
How Does Shotgun Mutagenesis Work?
1. Automated point mutation of every residue in the target protein to alanine
2. Native expression of individual mutants in human cells, enabling mapping of conformational epitopes
3. High-throughput expression, antibody reactivity, and functional testing
4. 3D structural visualization of the epitope
Applications of High-Resolution Epitope Mapping:
• Lead candidate selection by uncovering mechanisms of action
• MAb protection by strengthening IP
Epitope Mapping Project Deliverables:
• Assay Setup Report: Summary of optimized conditions for screening
• Final Report: Amino acid resolution epitopes and publication-ready figures
Shotgun Mutagenesis Epitope Mapping Case Studies
• Click here to see how Novartis characterized the mechanism of action for CXCR2 antibodies
• Click here to see how Covagen distinguished HER2 antibodies from existing therapeutics
• Click here to learn how epitope mapping enhances antibody protection
Select Publications Featuring Shotgun Mutagenesis Epitope Mapping
• Dussupt et al., 2020. Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor. NATURE MED 26, 228-235.
• Zhang et al., 2018. Mxra8 is a receptor for multiple arthritogenic alphaviruses. NATURE 557, 570-574.
• Zhao et al., 2017. Immunization-elicited broadly protective antibody reveals Ebolavirus fusion loop as a site of vulnerability. CELL 169, 891-904.
• Davidson and Doranz. 2014. A high-throughput shotgun mutagenesis approach to mapping B-cell antibody epitopes. IMMUNOLOGY 143(1), 13-20.
• Fong et al., 2014. Exposure of epitope residues on the outer face of the Chikungunya virus envelope trimer determines antibody neutralizing efficacy. J VIROL 88(24), 14364-14379.
• Paes et al., 2009. Atomic-level mapping of antibody epitopes on a GPCR. J AM CHEM SOC 131(20), 6952-6954.
Lipoparticles are virus-like particles that concentrate and present conformationally intact membrane proteins on non-infectious particles. This enables complex membrane proteins to be manipulated as soluble, high-concentration proteins for antibody immunization and screening.
The Lipoparticle ‘Advantage’ for Antibody Discovery:
• Lipoparticles concentrate proteins at 10-100× (~50-200 pmol/mg) the concentration of cells or membrane preps, resulting in robust immune responses and more successful antibody screens
• Lipoparticles display properly folded membrane proteins in their native cellular membrane, providing the ability to elicit and screen for conformational, functional antibodies
• Lipoparticles are ~150 nm, the size of most viruses, so are optimal targets for dendritic cells in vivo and surface attachment for phage display
Applications of Lipoparticles include:
• Phage/yeast display
• Antibody screening by ELISA
• Kinetic analysis by biosensor
• Radioligand and fluorescent binding assays
• Lipoparticles are typically customized to incorporate customer specified membrane proteins
• Each Lipoparticle batch is assessed using rigorous quality-control metrics to ensure homogeneity, purity, and target protein integrity
• Hundreds of membrane proteins have been successfully incorporated into Lipoparticles, which can be modified with biotin or fluorescence for detection
Pre-validated Lipoparticles contain optimized, highly expressed membrane proteins and are available for rapid delivery.
ReadyReceptor Lipoparticles are produced and validated using the same stringent quality metrics employed for Custom Lipoparticle production.
See all ReadyReceptor Lipoparticles.
• Learn how Lipoparticles rescued a CX3CR1 discovery campaign and enabled a clinical stage antibody
• Learn how Argenx used Lipoparticles to isolate antibodies with diverse epitopes against the GPCR glucagon receptor
• Learn how AdAlta used our CXCR4 Lipoparticles to isolate i-bodies
• Learn how Pfizer used Lipoparticles to target the CXCR4 pathway in leukemia
Select publications that feature Lipoparticles
• Tucker ET AL. 2018. Isolation of state-dependent monoclonal antibodies against the 12-transmembrane domain glucose transporter 4 using virus-like particles. PNAS 115(22):E4990-E4999.
• Fong ET AL. 2014. Exposure of epitope residues on the outer face of the Chikungunya virus envelope trimer determines antibody neutralizing efficacy. J VIROL 88(24)14364-14379.
• Willis ET AL. 2008. Virus-like particles as quantitative probes of membrane protein interactions. BIOCHEMISTRY 47(27):6988-6990.
• Endres ET AL. 1997. Targeting of HIV- and SIV-infected cells by CD4-chemokine receptor pseudotypes. SCIENCE 278(5342): 1462-1464.
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Integral Molecular has not received any endorsements.