Michael A. Barry, Ph.D.

Gene-based Vaccines
In gene therapy, the goal is generally to express transgene products that either replace the function of a missing protein or modify the activity or location of the protein in the body. An alternate approach, known as genetic immunization, is to deliver transgene products that do not confer function, but rather act as targets for the immune system. Genetic immunization is usually performed by introducing naked, simple DNA into the host by direct injection, or by using a gene gun. Because single or a subset of pathogen genes are used, genetic immunization avoids the risk of live vaccines while enjoying the advantages of mimicking a real infection by expressing antigens intracellularly. This mimicry occurs because antigens are produced intracellularly and can be presented by MHC I molecules to activate cytotoxic T lymphocytes to clear intracellular pathogens.

We are currently interested in the development of gene-based vaccines that drive mucosal immune responses to combat the 90% of pathogens that enter by this route. These efforts include the development of dendritic cell and mucosal targeting vaccine vectors, enteric-coated capsule testing, and imaging to evaluate vector and vaccine delivery in living animals.

Cell-targeting Technologies
For any drug, vaccine, or gene therapy application, the ultimate goal is to target these agents to the cells in need of detection or therapy while avoiding delivery into non-target tissues. While this is the goal, most agents do not specifically target the cells we want and frequently mistarget into problematic tissues reducing detection or therapy and increasing dangerous side effects.

Given these problems, we are interested in:

1. Developing high throughput systems to identify cell-targeting ligands to target drugs, diagnostics, and gene delivery vectors;
2. Developing high throughput and genetic technologies to translate cell-targeting ligands onto gene therapy vectors; and
3. Developing effective methods to track and screen cell-targeting ligands, cell-targeting vectors, and genetically-modified cells by imaging in living animals.