Carolina researchers are working to figure out how to fix the broken part of a human cell.
The work--gene therapy research--is intricate, marked by inscrutable milestones. While success remains far off, gene therapy holds a vast promise: cures for diseases such as cystic fibrosis, AIDS and cancer.
Gene therapy research is the focus of a center at Carolina authorized in February by the UNC system's Board of Governors. The center is working to coordinate a variety of gene therapy activities at Carolina and to help researchers build upon each others' discoveries.
The Gene Therapy Center is focusing on basic science questions in gene therapy research, said Jude Samulski, center co-director.
A recent National Institutes of Health report on the status of gene therapy research said researchers needed to put more emphasis on basic science and also to develop better ways to apply findings to possible treatments.
Those twin goals have been the focus of the gene therapy center since plans were formulated more than three years ago, said Samulski, professor of pharmacology.
"UNC's center is trying to go from step one to the very end," Samulski said. "At this point in time, we will put most of our emphasis on the basic science. As the technology evolves and the science evolves, the emphasis will shift toward the clinic."
High hopes
Carolina's gene therapy center differs from other centers around the country because it is focusing so intently on basic science questions, Samulski said.
"Our approach is that there are fundamental, basic questions that need to be resolved," he said. "If they are resolved, then they may apply to any disease."
Gene therapy, a field that's only 5 years old, involves identifying a gene that causes a certain disease or medical condition and replacing it with a corrected gene.
Scientists at Carolina and around the world are trying to figure out how to get replacement genes into the right cells. Most of the researchers are using viruses, carefully altered to contain the replacement gene, to deliver that gene into the body.
Samulski compared the state of gene therapy research to that of the early days of computers when machines the size of a small house were needed to perform calculations that today are carried out by simple pocket calculators.
"It took more than 30 years for computers to become usable and widely available," Samulski said.
"We're now sitting on one of those bluffs," he said. "We can look all the way down and see where one day we will be able to remove genetic diseases from the clinic.
"The question we're left with is: How long is it going to take?" he said.
Disappointing successes
For people with cystic fibrosis, Samulski's question becomes the difference between living and dying.
Cystic fibrosis is an inherited disease that kills most of its victims before they turn 30. As a result of this disorder, a person's lungs contain a sticky secretion that traps infections which eventually destroy the lungs.
Scientists around the world have been searching for more effective treatments for the disease, which also is called CF. Carolina scientists are leading the way in applying gene therapy techniques in designing potential CF treatments.
A UNC experiment last year with 12 young adults with cystic fibrosis demonstrated that while great strides have been made in gene therapy in the past five years, they seem ploddingly slow to some.
In the study, researchers used a common cold virus altered to carry the corrected CF gene. They administered a solution containing the virus into the nostrils of the patients. While tests showed that cells along the patients' airways accepted a very small amount of the corrected genes, the transfer was not at rates high enough to be effective.
"The CF trial generated a lot of enthusiasm and a lot of people were thinking, `This is going to save my kid if they get this working,'" Samulski said.
"The results disappointed the people with the highest expectations," he said. "But for the scientific community, it pointed us toward the next hurdle."
Taking a different route
The Gene Therapy Center will involve scientists from the schools of Medicine and Pharmacy and the Department of Biology. It will use facilities in the Thurston-Bowles buildings, Wilson Hall and UNC Hospitals.
The center's planning document projects a budget of just more than $1 million annually for the next five years. Samulski said the estimates were conservative and the center would work hard to attract grant support beyond the current projections.
"The center will help give our efforts a focus and allow us to go out and generate interest in our work and support for it," he said.
The center will have co-directors, with Samulski leading the basic science research and another co-director leading the clinical research. Richard Boucher, director of UNC's Cystic Fibrosis Research Center and one of the leaders of the CF gene therapy work, will serve as interim co-director of the center during a search for a permanent co-director.
By taking a deliberate approach to answering the basic science questions involved in gene therapy, the center's work may not grab the early headlines, but might hit a bigger payoff later, Samulski said.
"Let's say from the CF trial what we learned was that the virus that was delivering the gene had difficulty getting into the cell that we want to correct," he said. "There's a basic, fundamental problem--how do we get it into that cell?"
He said once that problem is solved, the solution, or a variation of it, should apply to other diseases.
From start to finish
While the answers to basic questions are sought, the UNC center also has the facilities to take potential treatments from the laboratory to the patient.
The center has access to different facilities where the altered viruses--called vectors--can be developed, mass-produced, tested in animals, certified by the federal government and tested in hospital patients, Samulski said. Each of those steps involves teams of researchers tackling their own set of difficult problems.
"The whole point of the Gene Therapy Center is that all along that pathway we will have feedback loops," he said.
If a vector that looked promising in the test tube can't be mass-produced, then the researcher doing the testing can find out right away and change course. Likewise, if a vector that has been mass-produced for animal experiments turns out not to be effective in animals, scientists earlier in the chain of development might change their strategies.
"If we try to do this just among interested colleagues, it's difficult to pull all these people together with the intensity to get something into the clinic," Samulski said. "Under the domain of the center, everyone's convened under one group."
Scientists from around the country and from as far away as Singapore have visited the center to see how it was being set up, Samulski said.
"Our highest compliment is the compliment you get from your colleagues," he said. "At this point in time, everybody's agreeing this is a logical and good approach."
To the UNC Home Page