Array Based Affinity Selection
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Principal Investigator: BRIAN KENNETH KAY Organization: TANGO BIOSCIENCES, INC. Fiscal Year: 2020 Award: $183,318 Funding agency: National Institute of General Medical Sciences Project Summary Funds are requested to apply technologies being developed in a current NIGMS award to generate recombinant antibody-like affinity reagents to the spike protein of the SARS-CoV-2 virus. As a proof-of-principle experiment, we have already isolated four fibronectin type III (FN3) monobodies that bind with low nanomolar affinity to the receptor binding domain (RBD) of the viral spike protein. An administrative supplement will permit continuation and expansion of this work to generate affinity reagents that bind with picomolar affinity and can be used in sensitive, robust diagnostic assays (homogenous assays, lateral flow assays) for virus particles in saliva. Separately, these monobodies will be reformatted as bivalent Fc fusions and overexpressed in CHO cells. Such reagents have the potential to serve as therapeutic agents that lower or block viral entry into patients ACE2-expressing cells. 1 Terms: <2019 novel coronavirus><2019-nCoV><ARNT><ARNT gene><Administrative Supplement><Affinity><Animals><Antibodies><Arizona><Aryl Hydrocarbon Receptor Nuclear Translocator><Assay><Award><Binding><Bioassay><Biologic Assays><Biologic Sciences><Biological Assay><Biological Sciences><Bioscience><Body Tissues><CDK2><CDK2 gene><CHO Cells><COP9 Signalosome, Subunit 5><COPS5><COPS5 gene><CSN5><Cancer Cause><Cancer Etiology><Cancers><Cell Body><Cell Division Kinase 2><Cells><Chimera Protein><Chimeric Proteins><Chinese Hamster Ovary Cell><Cold-Insoluble Globulins><Collaborations><Complex Mixtures><Contract Services><Cyclin-Dependent Kinase 2><DNA Alteration><DNA Sequence Alteration><DNA mutation><Diagnostic><Dioxin Receptor, Nuclear Translocator><Domestic Rabbit><Ensure><FN1><Family><Fibronectin 1><Fibronectins><Funding><Fusion Protein><GTP><GTP Phosphohydrolases><GTPases><Gene Transcription><Generations><Genetic Diseases><Genetic Transcription><Genetic mutation><Glass><Goals><Guanosine Triphosphate><Guanosine Triphosphate Phosphohydrolases><Guanosinetriphosphatases><HIF-1 Beta Gene><HIF-1Beta Gene><HIF-1beta><HIF1-Beta Gene><HIF1B><HIF1B Gene><HIF1Beta><HIF1beta Gene><Human><Human Cell Line><Human Engineering><Human Genome><Hypoxia-Inducible Factor 1 Beta Gene><Hypoxia-Inducible Factor 1, Beta subunit><Immunization><Immunochemical Immunologic><Immunologic><Immunologic Sensitization><Immunologic Stimulation><Immunological><Immunological Sensitization><Immunological Stimulation><Immunologically><Immunologics><Immunostimulation><In Situ><In Vitro><Individual><JAB1><Jun activation domain-binding protein 1><LETS Proteins><Large External Transformation-Sensitive Protein><Lateral><Libraries><Life Sciences><Location><MOV34 Family, 38-KD Member><Malignant Neoplasms><Malignant Tumor><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Methods><Mice><Mice Mammals><Modeling><Modern Man><Molecular Interaction><Monomeric G-Proteins><Monomeric GTP-Binding Proteins><Murine><Mus><NIGMS><National Institute of General Medical Sciences><Nuclear Translocator Gene Dioxin Receptor><Opsonic Glycoprotein><Opsonic alpha(2)SB Glycoprotein><Oryctolagus cuniculus><Pathway interactions><Patients><Phage Display><Pharmaceutical Agent><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phase><Plasmids><Process><Property><Protein Array><Protein Family><Proteins><Proteome><Protocol><Protocols documentation><PubMed><Publications><RNA Expression><Rabbits><Rabbits Mammals><Reagent><Recombinant Antibody><Recombinants><Recovery><Research><Research Resources><Resources><Route><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><SGN5><STTR><Saliva><Scaffolding Protein><Scientific Publication><Sequence Alteration><Severe acute respiratory syndrome coronavirus 2><Slide><Small Business Technology Transfer Research><Small G-Proteins><Small GTPases><Specificity><Spottings><TANGO><Technology><Therapeutic><Therapeutic Agents><Time><Tissues><Transcription><Translating><Translations><Universities><Viral><Virion><Virus><Virus Particle><Work><Wuhan coronavirus><alpha 2-Surface Binding Glycoprotein><base><commercial application><diagnostic assay><experience><experiment><experimental research><experimental study><genetic condition><genetic disorder><genomic alteration><guanosinetriphosphatase><human whole genome><malignancy><member><method development><milligram><mutant><nano-molar><nanomolar><neoplasm/cancer><novel><overexpress><overexpression><pathway><protein purification><receptor binding><receptor bound><screening><suicide substrates>