# Triple humanized ACE2-TMPRSS-FcGRT mouse models for COVID research in the C57BU6 and BALBIc backgrounds.

> **NIH NIH R44** · SYNBAL, INC. · 2023 · $566,896

## Abstract

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.

## Key facts

- **NIH application ID:** 10573272
- **Project number:** 5R44AI157900-03
- **Recipient organization:** SYNBAL, INC.
- **Principal Investigator:** Kurt Jarnagin
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $566,896
- **Award type:** 5
- **Project period:** 2021-05-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10573272

## Citation

> US National Institutes of Health, RePORTER application 10573272, Triple humanized ACE2-TMPRSS-FcGRT mouse models for COVID research in the C57BU6 and BALBIc backgrounds. (5R44AI157900-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10573272. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*