Researchers Receive $1.4M to Study Gene Therapy and DNA Delivery

Dec. 2, 2014

Since its discovery several decades ago, gene therapy has been a medicinal sphinx, with doctors as enamored by its potential as they are frustrated by the riddles it presents.
Researchers at the University of Rochester Medical Center are working to solve one of those riddles.
In order for gene therapy to be effective, doctors must discern how to deliver DNA to a cell’s nucleus, which requires a comprehensive understanding of how DNA and proteins move through cell cytoplasm. Knowledge of this system could lead to huge leaps in gene therapy effectiveness, and could potentially allow researchers to push forward on research into many currently-untreatable diseases.
The research is supported by a 4-year, $1.4 million grant from the National Institutes of Health.
“One of the best examples is cystic fibrosis,” said David A. Dean, Ph.D., professor of Pediatrics and Neonatology at URMC and the study’s lead researcher. “For cystic fibrosis, we know what the affected gene is, and we know what the mutation is. We know the physiology. The road block is the delivery — getting the corrective DNA in there and to the right cells for the right amount of time.”
Once DNA enters a cell, it still needs to travel to the nucleus, where it can influence a cell’s decision-making and response to diseases. To travel through a cell’s cytoplasm, the DNA bonds with proteins, which then ferry it to the cell’s center through microtubules that lead to the nucleus.
Dean and his team are researching which microtubules the DNA can use to reach the nucleus, and which proteins it can bond with to travel most efficiently. This means studying the more than 300 proteins within a cell to determine which ones drive DNA delivery.
“In a car, certain people and parts play bigger roles than others,” said Dean. “So if we remove the passenger protein, the car will still drive. But if we remove the driver, then it won’t, and then we’ll know that protein is the one steering the delivery.”
The research will also include a study of how the DNA moves around once it is within the nucleus itself.

Dean’s lab also studies lung disorders and acute lung injury, the latter of which results in fluid buildup in the lung and is often fatal. A better understanding of DNA delivery may also lead to better treatments for this type of injury.