Michael A. Barry, Ph.D.

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SUMMARY

The laboratory of Michael A. Barry, Ph.D., uses genes and viruses to treat a set of challenging diseases. The goals of the program are the development of:

• In vivo molecular and viral therapies.
• Cell-targeted molecular therapies.
• Treatments that stimulate or avoid the immune system:
  • Stimulating the immune system to treat viral infections and cancer.
  • Avoiding the immune system for gene therapy and shielding vectors themselves.

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. Current work uses adenovirus (Ad), adeno-associated virus (AAV) and lipid nanoparticles (LNPs). The lab currently works on propionic acidemia gene therapy and gene therapies for genetic kidney diseases. An AAV gene therapy for propionic acidemia is being advanced to a phase 1 clinical trial with the Center for Individualized Medicine at Mayo Clinic.
• 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 have not 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, CMV, Zika, MRSA, Clostridium difficile, cancer and SARS-CoV-2 (the COVID-19 virus). The team's most recent efforts have been in developing a novel replicating Ad platform called single-cycle Ad (SC-Ad). SC-Ads replicate transgenes thousands of times. SC-Ads also produce up to 100 times more transgene protein than do benchmark replication-defective Ads (RD-Ads), which are in phase 1 testing against SARS-CoV-2 (NCT04839042).
• 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 not only to kill cells, but also to express immunostimulatory proteins to make tumors "hot." There are more than 100 different serotypes of Ads. So the lab taps into the different biologies of these viruses to avoid neutralizing antibodies and target various cancers. Several of these native and retargeted CRAds are being advanced to clinical trials.
• Basic virology, immunology and pharmacology. Sometimes it works to reengineer viruses as therapies, and 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 Ad, AAV and LNP therapeutics. More recently his team is working on filovirus and orthomyxovirus virology as well as leveraging these viruses for translation to help humans.

Significance to patient care

Dr. Barry and his team's work on gene therapy addresses diseases that have no other treatment options, so advances in this area are likely to greatly improve the quality of life and survival of patients of all ages.

Infectious diseases are one of the greatest worldwide causes of death in humans. Dr. Barry's work targets vaccines against pandemic infectious diseases. So progress in these efforts appears promising to prevent these diseases and stop their spread.

Metastatic cancer is a profound challenge to current treatments. The lab's efforts to deliver self-amplifying virotherapy hold promise to attack disseminated cancer, providing another weapon in the arsenal of treatment options for patients.