DURHAM, N.C. -- Duke University Medical Center researchers report that they have modified a common virus so that it can carry corrective genes to defective cells without stimulating an immune response.
They believe their achievement overcomes a major barrier to widespread use of adenovirus, a common cold virus, as a genetic delivery vehicle.
Their results were published in the February issue of the journal Human Gene Therapy. The research was supported by grants from the National Institutes of Health, the Muscular Dystrophy Association and the Howard Hughes Medical Institute.
"In our set of experiments, we were not only able to deliver the gene to the intended site, but it also persisted for more than two months," said Dr. Andrea Amalfitano, a Duke pediatric geneticist who led the team. "If our approach is confirmed by further studies, these modified adenoviruses could have great application for future gene therapy in humans." Also on Amalfitano's research team were Duke's Huimin Hu, Ph.D. and Delila Serra.
Scientists have long recognized that the ubiquitous adenovirus offers many advantages as a "vector" for gene therapy. It can carry practically any size gene, it can infect virtually all cells in the body, and it can be easily mass-produced. However until now, within two to three weeks of the virus's introduction into the body, the immune system of recipients easily recognized the virus and its gene payload as foreign and cleared it from the body, as well as the cells the virus had infected.As a result of their findings, the Duke scientists propose a "two-hit" hypothesis to explain why other adenovirus vectors usually failed.
The first immune-system "hit" after an adenovirus infection comes when the
animal's immune system recognizes the virus as foreign and attacks it,
Amalfitano said. The second "hit" comes when the immune system then recognizes
the introduced gene, called a transgene, as fore
Contact: Richard Merritt
Duke University Medical Center