A novel strategy for circumventing safety problems that have plagued gene therapy has been offered by a complex multicenter group of researchers, including Professor Claudio Napoli, a Full Professor at the II University of Naples and Adjunct Professor at the Sbarro Research Institute for Cancer Research and Molecular Medicine and the Center of Biotechnology at the College of Science and Technology of Temple University.
The study was published online in the prestigious scientific journal Cell (Cell 2008 Feb 8;132:397-409).
The study reports that adenovirus type 5, a common vector for delivering gene therapy, transfects liver cells by a different mechanism than previously thought. That mechanism offers a new target for modifying the viral vector to make it safe for clinical use.
A number of studies indicated that it would be possible to use adenovirus as a vector to deliver genes into specific locations, such as a solid tumor. But when it's injected intravenously, the virus accumulates in the liver instead of circulating in the body, raising the risk of toxicity and transfection of other cells. Basically, adenovirus consists of three major proteins - fiber, penton and hexon. Based on earlier work, most researchers held that the main mechanism of viral transduction was the fiber protein's interaction with a receptor on the target cell. But attempts to mutate the fiber protein did not block the virus's accumulation in the liver in vivo.