UF establishes national center for gene therapy studies

Scientists from across the country soon will be calling on University of Florida researchers to conduct safety tests of promising gene therapies for a variety of diseases.

UF’s new National Gene Vector Laboratory Toxicology Center will serve as a referral site for researchers who need comprehensive animal studies completed before moving on to human tests. The center, one of only two in the country, is supported by a new five-year, $2.4 million grant from the National Center for Research Resources, a component of the National Institutes of Health.

“Without this kind of a resource, most researchers funded by the NIH would not have a way to push their studies forward,” said Terence R. Flotte, M.D., director of UF’s Genetics Institute and the Powell Gene Therapy Center.

“What most scientists do is initially test their gene therapy in a very small number of animals and look to see if it has an effect on the disease,” Flotte said. “That’s an important proof-of-concept study. But the treatment cannot be tested in people until more formal toxicology studies have been done in a large number of animals. If an adverse effect occurs in only 5 percent of animals treated, the initial study may not have included enough animals to reveal that problem.”

Gene therapy involves inserting thousands of copies of a gene in a particular location of the body in an attempt to reverse a disease or minimize its effects. The therapy is not designed to introduce genetic changes that can be passed along to subsequent generations but rather to provide a patient with working and activated copies of a needed DNA sequence.

UF and the Southern Research Institute, a nonprofit organization affiliated with the University of Alabama at Birmingham, were the only two centers funded through the competitive application process. The grant will support equipment purchases and personnel to conduct the studies.

Flotte said he expects two to five animal research projects will be assigned to UF each year by a steering committee of the NIH-supported National Gene Vector Laboratories. Flotte is a member of the panel.

For each study, UF scientists will administer the gene therapy, assess its effectiveness on disease and evaluate animals carefully for any signs of adverse effects. UF staff also will provide statistical and data-management support.

UF was well-positioned to compete for the grant. The university is home to a core group of researchers who pioneered the use of the apparently harmless adeno-associated virus as a vehicle for ferrying copies of corrective genes into selected tissues. AAV is widely considered to be among the most promising gene therapy vectors.

The university also has an established team that conducts animal studies. The team was organized to advance UF research to clinical testing, including efforts to begin trials of gene therapy for an inherited lung disease, alpha-1-antitrypsin deficiency, and for a rare cause of blindness, Leber congenital amaurosis.

Key players in the new center include James M. Crawford, M.D., Ph.D., chairman of UF’s department of pathology, immunology and laboratory medicine; Martha Campbell-Thompson, D.V.M., Ph.D., an assistant research professor in Crawford’s department; Ron Marks, Ph.D., a professor of biostatistics; and Amy E. Poirier, a researcher in Flotte’s lab.