IOWA CITY, Iowa -- Gene transfer is a promising strategy that may eventually help to reverse or prevent many diseases, but in some cases there are glitches that must first be worked out.
A University of Iowa Health Care research team has found one possible way to eliminate a gene transfer hang-up related to cystic fibrosis. The researchers, led by Michael Welsh, M.D., UI professor of internal medicine, and physiology and biophysics, and a Howard Hughes Medical Institute investigator; David Wiemer, Ph.D., UI professor of chemistry; and John Lee, M.D., a UI otolaryngology resident, have found a way to make an essential binding process more effective.
Gene transfer involves using a vector, often a disabled cold virus, as a delivery vehicle to supply cells with healthy copies of flawed genes. For cystic fibrosis, this means delivering a normal copy of the cystic fibrosis gene to cells lining the bronchial airways. However, researchers have had difficulty getting the vectors to stick to the cells.
"The major problem is that the viruses we use to carry in a gene don't bind very well to the airway cells," Welsh said. "The first challenge is to improve binding."
There are two ways to solve the binding problem, Welsh explained. Researchers can either change the delivery vehicle (the vector) or change the recipient cell so viruses can bind to it.
"Most of the effort has been focused on the former, trying to modify the vector," Welsh said. "We decided to take a look at the latter, to modify the cell surface."
The researchers decided to alter the cell surface with a sugar because cells tolerate a wide variety of sugars and incorporate them into surface proteins. However, the researchers needed a novel sugar, one that would stand out as unique on the cell surface and which could serve as a molecular handle for attaching to the vector. This need led to collaboration with Wiemer in the UI Department of Chemistry. Wiemer's lab created a synthetic suga
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Contact: Jennifer Cronin
jennifer-cronin@uiowa.edu
319-335-9917
University of Iowa
26-Oct-1999