SUMMARY
The Virology, Vector and Vaccine Engineering Laboratory of Michael A. Barry, Ph.D., uses genes and viruses to treat a set of challenging diseases. The program seeks to develop in vivo molecular and viral therapies and cell-targeted molecular therapies. The program also seeks to develop therapies that stimulate the immune system to treat viral infections and cancer.
Focus areas
- Gene therapy. For many genetic diseases, researchers know which genes are affected. The challenge is to replace these genes efficiently and safely with their functional counterparts. Dr. Barry's lab is largely agnostic to which vectors to use. The lab currently uses adenovirus, adeno-associated virus and lipid nanoparticles. A phase 1 clinical trial for our adeno-associated virus gene therapy for children with propionic acidemia, a metabolic disease, should begin in 2025 in partnership with the Center for Individualized Medicine. We also are showing good promise in molecular therapies for Alport syndrome, which is caused by mutations in collagen 4 genes. Since Alport syndrome and collagen 4 mutations may affect up to 1% of patients, these therapies could help many people.
- Gene-based vaccines. Vaccines are among the more cost-effective medical interventions available. Most vaccines consist of inactivated or damaged versions of a pathogen. While these traditional approaches can be potent, they haven't been able to control some of the most devastating infectious agents. So other approaches are needed. Dr. Barry's lab has developed vaccines against a broad range of viruses and diseases, including HIV-1, influenza, hepatitis C virus, cytomegalovirus, Zika, methicillin-resistant Staphylococcus aureus, Clostridium difficile, cancer and SARS-CoV-2 (the COVID-19 virus).
We developed a novel single-cycle adenovirus COVID-19 vaccine that went into phase 1 clinical testing in 2021 (NCT04839042). This vaccine was unique in being tested not only via the standard intramuscular route but also via the intranasal route where the COVID-19 virus infects humans. The single-cycle adenovirus platform was licensed to Tetherex Pharmaceuticals Corp. in 2020 and spun off into a new company called Moat Biotechnology. The lab also generates vaccines against potential next-generation pandemics and has recently made vaccines against Marburg virus and pandemic influenza.
- Oncolytic immunotherapy viruses. Oncolytic viruses have been pioneered by several field leaders in the Department of Molecular Medicine at Mayo Clinic. Dr. Barry's lab works in this area using conditionally replicating adenoviruses (CRAds). These viruses are used to not only kill cells but also express immunostimulatory proteins to make tumors "hot." There are more than 100 serotypes of adenoviruses. CRAd657 was licensed to Adze Biotechnology Inc. One CRAd657 expressing CD40L should enter clinical trials in 2025 for melanoma. It will support a clinical trial with the Center for Regenerative Biotherapeutics.
- Basic virology, immunology and pharmacology. Sometimes it works to reengineer viruses as therapies. Sometimes it doesn't. When things don't work as expected, new basic biology, virology, immunology or pharmacology questions arise that need to be pursued as hypothesis-driven research. These spinoffs are frequently more engaging than engineering viruses. Dr. Barry's lab performs this work using adenovirus, adeno-associated virus and lipid nanoparticle therapeutics. His team is working on filovirus and orthomyxovirus virology, as well as leveraging these viruses for translation to help humans. Work with the Ebola virus has spun off a novel, self-amplifying antiviral therapy that may allow protective therapeutic proteins to be delivered to at-risk cells to repel incoming viruses. We are testing its utility for Ebola virus and seeing if it also can work against persistent viruses such as HIV.
Significance to patient care
Dr. Barry and his team work on gene therapy for diseases with no other treatments. The team's work could greatly improve patients' quality of life and survival. The lab may soon help patients with propionic acidemia. Later, the lab may help patients with kidney diseases.
Infectious diseases are one of the greatest worldwide causes of death in humans. Dr. Barry's work targets vaccines against pandemic infectious diseases. Since COVID-19, new nonmessenger RNA vaccines have been created against bird flu, Marburg and Ebola viruses. They also have been created for clinical diseases such as C. diff, antibiotic-resistant bacteria and norovirus.
Cancer that spreads challenges current treatments. The lab's efforts to deliver self-amplifying virotherapy hold promise to attack cancer that has spread from the primary tumor area to other parts of the body. This will offer another treatment option for patients. These approaches look like they will be good partners with immune checkpoint and chimeric antigen receptor (CAR)-T cell therapies by firing up the immune system against the cancers.