Gene therapy tool would target free radicals
New method would make the most of the balance between the good and bad of free radicals
Gene therapy has been touted as a possible way to cure genetic diseases, but new research suggests that it could also fight the wear and tear that leads to cardiovascular diseases.
An excess of free radicals can cause damage that often contributes to heart disease and atherosclerosis (hardening of the arteries). But some kinds of free radicals also benefit cells by serving as signaling molecules that relay information as part of the cells’ normal operation.
To work within this delicate balance, researchers in Finland have developed a way to insert into human cells free radical–fighting genes that only get switched on when free radical concentrations are high. That way, the genes could stave off the worst effects of free radicals without inhibiting the molecules’ useful functions, the researchers report in the September Gene Therapy.
The technique “would be very useful in gene therapy because you have a more focused expression of what you want. It’s not on when it’s not needed,” comments Stefan Ryter of Brigham and Women’s Hospital and HarvardMedicalSchool in Boston. Ryter studies how the oxidative damage done by free radicals alters proteins and other molecules in cells, and how those changes are linked to disease . Seppo Ylä-Herttuala and colleagues at the University of Kuopio in Finland engineered a virus to carry an anti–free radical, or antioxidant, gene called heme oxygenase-1, or HO-1. To control when the gene is active, the researchers coupled it to a short piece of genetic code that normally controls when a different antioxidant gene in cells switches on and off. In experiments using human cells, the team showed that this combination could produce the protein encoded by HO-1 in response to oxidative stress caused by free radicals.