# Transient Gene Therapy as Broad Spectrum Antiviral

> **NIH NIH R41** · LAB11 THERAPEUTICS, LLC · 2021 · $255,932

## Abstract

Project Summary
Currently there are very few antiviral drugs, and no broad-spectrum antiviral drugs. For example, Influenza A
virus (IAV) causes 12,000-56,000 deaths and 150,000-750,000 hospitalizations annually in the US alone, despite
the availability of vaccines and five FDA-approved drugs 1, 2. Resistance to two of the five existing drugs has
already emerged 13. Second, SARS-CoV-2 a virus which causes COVID19 led to unprecedented death toll
worldwide. Currently there are no anti-SARS-Cov-2 drugs that can target other corona viruses.
Type I interferons (IFNs) are host cytokines providing protection against viral infections. There are several
different layers of IFN negative regulation, and the ISG15/USP 18 host protein 4, 5, 6, 7 complex is responsible for
suppressing the tail end of IFN inflammation. Human ISG15 knockouts have been identified and shown to control
IAV and SARS-CoV-2 replication better than WT counterparts.
Based on the evidence of efficacy and safety provided by these ISG15-deficient individuals, Lab11 Therapeutics
is developing new drugs, transient host-mimicking modified mRNA therapies aimed at enhancing control of IAV
and SARS-CoV-2 infection in the general population 4, 6, 7. Candidate drugs are recreating antiviral state identified
and tested in the human system, but, for FDA approval, Lab11 Therapeutics must demonstrate safety and
efficacy in an animal model, before proceeding with human in vivo studies.
This STTR aims to test our modRNA cocktail drugs in animal models of IAV and SARS-CoV2 infection. The
phase I hypothesis is that modRNA cocktail delivered intranasally will restrict IAV replication in mice and SARS-
CoV-2 infection in hamsters. We will test this hypothesis in Specific Aim 1, by evaluating the effects of modRNAs
on IAV in human and murine cell lines followed by in vivo testing in mice. In Specific Aim 2, we will evaluate the
effects modRNAs have on SARS-CoV-2 in human and hamster cell lines followed by in vivo testing in hamsters.
In Phase II, we propose to test different delivery modes and encapsulations of modRNAs to optimize the most
effective delivery and antiviral protection.
The global influenza market is valued at about 5 billion dollars, about a fifth of which relates to non-vaccine
products. The patient population targeted by Lab11 Therapeutics will be hundreds of millions of individuals in
the general population. Given the crucial role of IFN in the control of many viral infections (ISG15-deficient cells
control have been shown to control the replication of 14 different viruses more effectively than WT cells), the
lead drugs developed here for IAV and SARS-CoV2 are likely to be effective against other viral diseases too.
This will provide Lab11 Therapeutics with opportunities for the licensing of different products with identical
mechanisms of action on an indication-by-indication basis.

## Key facts

- **NIH application ID:** 10324302
- **Project number:** 1R41AI164999-01
- **Recipient organization:** LAB11 THERAPEUTICS, LLC
- **Principal Investigator:** Dusan Bogunovic
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $255,932
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10324302

## Citation

> US National Institutes of Health, RePORTER application 10324302, Transient Gene Therapy as Broad Spectrum Antiviral (1R41AI164999-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10324302. Licensed CC0.

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