Author: Doshi Ojus
Date: June 2007
Scientists are one step closer to correcting hearing disorders like deafness using genetic engineering. Last week, researchers at the University of Virginia, led by Dr. Jeffrey Holt, published a report in the journal Gene Therapy which outlined a method for potentially repairing damaged hair cells, the cells in ears responsible for converting sound into electrical signals, by using a virus.
"We used viral vectors, in particular adenovirus, which causes the common cold, but we've engineered it to stop it from making people sick," said Holt, associate professor of neuroscience and otolaryngology at UVA. Instead, his group genetically modified the virus to produce a correct version of a gene called KCNQ4 that had gone awry in diseased auditory tissue. Through a process called transfection, the virus introduces its genetic material into the hair cell genome, and the host cells produce whatever is found on the viral DNA,in this case, the undamaged version of KCNQ4.
Holt's team incorporated Green Fluorescent Protein, or GFP, into the virus's genetic material in order to visually detect the viral genome, and when the hair cell specimens fluoresced bright green, they knew the adenovirus targeted hair cells specifically.
The gene KCNQ4, which, in its unmutated form, creates a potassium channel protein, was no stranger to Holt and his colleagues. "Our lab has been particularly interested in it for a while. We've been studying it in the mouse inner ear, and we know it causes deafness in humans, so it was a natural target," he explained.
The group's method provides an important way to modify the genome of damaged cells. Holt mentioned that another group published a paper in 2005 showed that similar methods could be used in guinea pigs. "They showed using an adenovirus that they could put a gene in the inner ears of deaf guinea pigs and restore hearing function," Holt said. "Our work shows that andenovirus can transfect human hair cells. The next step is to combine techniques and see if we can correct deafness in humans."
Written by Ojus Doshi