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 the vectors themselves
Dr. Barry's lab tests these approaches in the following areas:
- Single-cycle adenoviruses. In contrast to replication-defective vaccines, the single-cycle vector amplifies one copy of DNA up to 10,000 times in every cell. This can produce as much as 100 times the antigen as a replication-defective vector. Dr. Barry's lab has been engineering new ways to get genes into cells and amplify those genes and the proteins that they produce. They've most recently applied this to SARS-CoV-2 using novel vaccine vectors called the single-cycle adenovirus platform. Read more.
- Gene therapy. For many genetic diseases, researchers know which genes are defective. The challenge is to efficiently and safely replace these defective genes with their functional counterparts. Dr. Barry's lab is largely agnostic to which vectors to use. They currently work on propionic acidemia gene therapy (affecting every cell in the body) and gene therapies for genetic kidney diseases.
Gene-based vaccines. Vaccines are one of the most 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. In these cases, Dr. Barry's lab is also using genes as drugs. However, instead of trying to fix a defective gene, they are delivering single genes from pathogens to vaccinate against them. Because only a subset of pathogen genes are used, gene-based vaccines avoid the risk of infection from live vaccines while mimicking a real infection and achieving subsequent protection.
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). Their most recent efforts have been in developing a novel replicating adenovirus (Ad) platform called single-cycle Ad (SC-Ad). SC-Ads replicate transgenes thousands of times and produce up to 100 times more transgene protein than do benchmark replication-defective Ads (RD-Ads) that are in advanced testing against the COVID-19 virus.
Oncolytic immunotherapy viruses. The goal for gene therapy and vaccines is to deliver genes to cells and have the cells survive. For this reason, Dr. Barry and colleagues use tamed versions of viruses to deliver genes for gene therapy or gene-based vaccines. For cancer therapy, the goal is to kill cells. For this application, they modify the viruses to kill cancer cells but protect normal cells. These anti-cancer viruses have the appeal of being "self-amplifying" drugs because each cancer cell that is killed can, in turn, produce thousands of new anti-cancer viruses that can spread to other cancer sites. Therefore, these self-amplifying drugs can infect one cancer site and spread. Dr. Barry's lab hopes this may be useful to treat cancers that have spread locally or metastasized throughout the body.
Dr. Barry's lab has tested a number of viruses against many types of cancer, including prostate, breast, ovarian and B cell cancers. Interestingly, they have found that different viruses appear to have different appetites for killing different types of cancers. These naturally "hungry" serotypes have been armed with up to three immunotherapy checkpoint payloads or cancer antigens and are being tested for efficacy against several cancer types.
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 holds promise 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.