Document text
Principal Investigator: Dusan Bogunovic
Organization: LAB11 THERAPEUTICS, LLC
Fiscal Year: 2021
Award: $255,932
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Animal Model><Animal Models and Related Studies><Animals><Antiviral Agents><Antiviral Drugs><Antiviral resistance><Antiviral resistant><Antivirals><Biological Function><Biological Process><Biotech><Biotechnology><COVID-19><COVID-19 infection><COVID-19 virus><COVID19><COVID19 infection><COVID19 virus><CV-19><CV19><Cell Body><Cell Line><CellLine><Cells><Cessation of life><CoV-2><CoV2><Complex><Coronaviridae><Coronavirus><Cricetinae><DNA Therapy><Data><Death><Development><Dose><Drugs><Emergencies><Emergency Situation><FDA approved><Formulation><Gene Transfer Clinical><General Population><General Public><Genes><Genetic Alteration><Genetic Change><Genetic Intervention><Genetic defect><Germ-Line Mutation><Germline Mutation><Goals><Grippe><Hamster Cell Line><Hamsters><Hamsters Mammals><Hereditary><Hereditary Mutation><Hospital Admission><Hospitalization><Human><Human Cell Line><IFN><ISG15><ISG15 gene><Immune system><In Vitro><Incidence><Individual><Infection><Inflammation><Influenza><Influenza A><Influenza A virus><Influenza Viruses Type A><Influenzavirus A><Inherited><Innate Immunity><Interferon Type I><Interferon-Induced Protein IFI-15K><Interferons><Knock-out><Knockout><Knowledge><Laboratories><Lead><Licensing><Maps><Medication><Messenger RNA><Mice><Mice Mammals><Modern Man><Morbidity><Morbidity - disease rate><Murine><Mus><Mutation><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Orthomyxovirus Type A><Outcome><Pb element><Pharmaceutic Preparations><Pharmaceutical Agent><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phase><Phase I Study><Preparedness><Proteins><Readiness><Regulation><Resistance><Role><SARS corona virus 2><SARS-CoV-2><SARS-CoV-2 infection><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><STTR><Safety><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 related corona virus 2><Small Business Technology Transfer Research><Strains Cell Lines><Symptoms><System><Tail><Target Populations><Technology><Testing><Therapeutic><Type A Influenza><Vaccines><Viral><Viral Diseases><Virus><Virus Diseases><Virus Replication><Vulnerable Populations><Work><Wuhan coronavirus><access to vaccination><access to vaccines><allergic/immunologic body system><allergic/immunologic organ system><anti-flu><anti-influenza><anti-viral agents><anti-viral drugs><anti-viral resistance><anti-viral resistant><anti-virals><antiflu><base><commercial application><corona virus><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 virus><cultured cell line><cytokine><developmental><drug candidate><drug/agent><flu><gene therapy><gene-based therapy><genetic therapy><genome mutation><genomic therapy><hCoV19><heavy metal Pb><heavy metal lead><high risk><in vivo><in vivo evaluation><in vivo testing><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><mRNA><medical college><medical schools><model of animal><model organism><mortality><nCoV2><nano particle><nano-sized particle><nanoparticle><nanosized particle><new drug treatments><new drugs><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel therapeutics><novel therapy><patient population><phase 1 study><phase 2 study><phase II study><resistance strain><resistant><resistant strain><school of medicine><social role><vaccination access><vaccination availability><vaccine access><vaccine availability><viral infection><viral multiplication><viral replication><virus infection><virus multiplication><virus-induced disease><vulnerable group>