Word: adenovirus
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Dates: during 1990-1999
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...used as packaging material for whatever gene the patient lacks. In Jesse's study, all 18 participants had the same disease: ornithine transcarbamoylase (OTC) deficiency, which slows the liver's ability to metabolize nitrogen and releases deadly ammonia into the bloodstream. So Wilson's team harnessed the adenovirus (a cause of the common cold), neutralized harmful elements and used the virus to send in normal copies of the gene that was defective in Jesse...
...early gene-therapy trial for cystic fibrosis, inflammation caused by the viral carrier, an altered adenovirus, was so severe that the FDA ordered a halt to the effort, casting a pall over all the other trials--and the field in general. More problems plagued the researchers. In many cases the implanted genes failed to "turn on," or express themselves, and were unable to command the cells to produce the protein they were supposed to provide. Some operated for a while and then inexplicably shut down...
Most researchers in the field agree that the adenovirus and retrovirus vectors are imperfect, to say the least. In addition to having immunological side effects, both lack the carrying capacity to accommodate the larger, more complex genes that would be useful in therapy. "There are only three problems in gene therapy," says Salk's Verma, "delivery, delivery and delivery. It isn't going to be a problem to make gene therapy work--if we have an appropriate set of tools to deliver the genes...
Many other vectors are now being tested. Dr. Ronald Crystal of New York Hospital-Cornell Medical Center was jogging one day when he had the inspired notion of delivering genes to the lungs of cystic fibrosis patients using the adenovirus that causes the common cold. "This is a virus that has taken millions of years to evolve to do what it does -- get into the lung," says Crystal, who plans to begin a new set of trials with the virus in the next month or so. One of his challenges is to render the adenovirus harmless and keep it from...