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Principal Investigator: Kurt Jarnagin
Organization: SYNBAL, INC.
Fiscal Year: 2022
Award: $1,000,000
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract Phase I/II
Synbal and the La Jolla Institute for Immunology (LJI) are combining efforts to create
breakthrough new tools for COVID-19 research to enhance research and drug development
for COVID-19 disease. We aim to create a state-of-the-art set of humanized mouse strains
susceptible to SARS-CoV-2, via the precision knock-in of a human mini gene at the mouse locus
in each of three loci. The clinical features of COVID-19 are poorly mimicked by the existing single
transgenic mouse models; those strains get a milder disease. In this SBIR Fast track PHASE I/II
grant, the team will humanize the ACE2 viral receptor, its co-infection protein TMRPSS2, and the
main antibody clearance receptor FCGRT to create double and triple humanized strains in
C57BL/6J and BALB/c backgrounds. These two backgrounds are Th1 responders and Th2
responders, respectively, and will allow modeling of the extreme variability of human pathology
observed in infected patients. The multiply humanized mice strains will be superior to the single-
gene transgenic models available to date; and, thus, will allow for better basic research and drug
development. To validate the strains, we plan to thoroughly characterize the effects of SAR-CoV-
2 infection at the clinical, virologic, histopathologic, and immunologic levels, and publish the
findings. The product strains created in this project, the triple humanized C57B6L/6J-
ACE2/TMPRSS2/FCGRT mice and the double humanized BALB/c-hACE2/hTMPRSS2 and
C57BL/6J-ACE2/TMPRSS2 mice will be made readily available for the academic and
pharmaceutical research communities through our animal vendor partner Jackson Labs or
Taconic Biosciences.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><7S Gamma Globulin><ACE2><Address><Animals><Antibodies><Antibody Response><Antiviral Therapy><BALB C Mouse><BALB/c><Basic Research><Basic Science><Biologic Sciences><Biological Sciences><Bioscience><Businesses><COVID><COVID-19><COVID-19 infection><COVID-19 predisposition><COVID-19 susceptibility><COVID-19 virus><COVID-19 vulnerability><COVID19><COVID19 infection><COVID19 virus><CV-19><CV19><Cell Body><Cell Mediated Immunology><Cell-Mediated Immunity><Cells><Cellular Immunity><Cellular Membrane><Clinical><CoV disease><CoV-2><CoV2><Communities><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 susceptibility><Coronavirus disease 2019 vulnerability><Data><Development><Development and Research><Disease><Disease model><Disorder><Drug Kinetics><ES cell><Embryo><Embryonic><Epitheliasin Gene><Fc Receptor><Generations><Genes><Genetic><Genomics><Grant><Human><Human Pathology><IgG><Immune response><Immunochemical Immunologic><Immunoglobulin G><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunology><Inbred BALB C Mice><Infection><Institutes><Journals><Knock-in><Life Sciences><Magazine><Manuscripts><Marketing><Mice><Mice Mammals><Modeling><Modern Man><Mouse Strains><Murine><Mus><PRSS10><Patients><Peer Review><Pharmaceutical Agent><Pharmaceuticals><Pharmacokinetics><Pharmacologic Substance><Pharmacological Substance><Phase><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Proteins><Publications><Publishing><R & D><R&D><Receptor Protein><Research><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 predisposition><SARS-CoV-2 susceptibility><SARS-CoV-2 vulnerability><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SBIR><Sales><Scientific Publication><Serine Endopeptidases><Serine Protease><Serine Protein Hydrolases><Serine Proteinases><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 predisposition><Severe acute respiratory syndrome coronavirus 2 susceptibility><Severe acute respiratory syndrome coronavirus 2 vulnerability><Severe acute respiratory syndrome related corona virus 2><Small Business Innovation Research><Small Business Innovation Research Grant><TMPRSS2><TMPRSS2 gene><Testing><Transgenic Mice><Transgenic Model><Transmission><Vaccines><Vendor><Viral><Viral Receptor><Virus><Virus Receptors><Writing><Wuhan coronavirus><angiotensin converting enzyme 2><angiotensin converting enzyme II><anti-viral therapy><antibody receptor><co-infection><coinfection><corona virus disease><corona virus disease 2019><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><developmental><disorder model><drug development><embryonic stem cell><extracellular><hCoV19><host response><humanized mice><humanized mouse><immune system response><immunoresponse><improved><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><knockin><mouse model><murine model><nCoV2><predisposed to Coronavirus disease 2019><receptor><receptor binding><receptor bound><research and development><stem cell of embryonic origin><susceptible to COVID-19><susceptible to Coronavirus disease 2019><susceptible to SARS-CoV-2><susceptible to Severe acute respiratory syndrome coronavirus 2><tool><transgenic trait><transmission process><vector><viral infectious disease treatment>