Gene therapy genes need 'off' switch: WA research investigates

 Gene therapy is a relatively new strategy that attempts to help injured brain cells survive and regrow and is being used to treat brain and spinal cord injury and neuro-degeneration. Image
THE alteration of nerve cell shape has been identified as a potential side effect of gene therapy.
The study, published in PLoS One, was led by Winthrop Professor Alan Harvey from UWA’s school of Anatomy, Physiology and Human Biology, and Associate Professor Jennifer Rodger, NHMRC Research Fellow in Experimental and Regenerative Neurosciences at UWA.
Gene therapy is a relatively new strategy that attempts to help injured brain cells survive and regrow and is being used to treat brain and spinal cord injury and neuro-degeneration.
Prof Harvey says his team has carried out work using modified viral vectors to introduce growth-promoting genes into injured nerve cells (neurons).
“We have looked at ways of protecting the neurons and getting them to regrow their nerve fibers after they are injured,” he says.
“But I had the concern that, using the current generation of commonly used vectors, the introduced gene is switched on all the time.”
“Once inside the cell, it’s likely that the new gene is constantly producing messages and constantly making its protein, which is not normally what happens with genes—they are switched on and off depending on when they’re needed.”
The team set out to determine what happened over a period of months to nerve cells in the retina that contained genes introduced by gene therapy, looking especially where the gene was “switched on” all the time and the protein, a growth factor, was being made consistently.
“There were changes in the shape of the processes of these cells over time,” Prof Harvey says.
“The changes varied depending on the type of growth factor gene that was introduced, but what was interesting was that the change didn’t only occur in the cells that contained the gene—the neighbouring cells changed as well, presumably due to secreted proteins present in the extracellular space,” he says.
Prof Harvey hopes this research raises a flag to what he says is an additional aspect that the gene therapy field really should be concerned about.
“If you are using these sorts of vectors and you can’t switch the gene off, then potentially that gene—if it’s making a protein that’s secreted into the extracellular space—may have all sorts of effects on those cells and on neighbouring cells,” Prof Harvey says
At this stage, the functional consequences of these findings are unknown.
“It is important to develop vectors where the expression of the introduced gene can be controlled, can be switched on or off when appropriate,” he says.