Gene therapy -- which aims to replace "bad" genes with useful ones -- has yet to live up to its promise largely because of problems delivering genes to the right place in the body. What's more, the viruses many gene therapy techniques use can arouse unwanted immune reactions.
Researchers at Jefferson Medical College have developed a system that sidesteps viruses, and they hope, some of the inherent problems with their use. Scientists, led by Eric Wickstrom, Ph.D., professor of microbiology and immunology, and graduate research assistant Stephen H. Cleaver, both of Jefferson Medical College and Thomas Jefferson University in Philadelphia, have used DNA and bacterial proteins to deliver a gene to a specific place in a piece of human DNA.
They have used a "transposon," or a naturally mobile piece of DNA, from the E. coli bacterium as a gene delivery vehicle, inserting a gene for antibiotic resistance into a segment of DNA.
"This is the first time it [gene therapy] was done this way," says Dr. Wickstrom, who is also a member of Jefferson's Kimmel Cancer Center. "The transposon inserted in exactly the right place and expressed its product - in this case, an antibiotic-resistant gene."
Their results appear August 22 in the journal Gene.
The technique has several advantages. "It avoids using viruses that cause immune reactions, it puts the gene in a precise, known location as opposed to anywhere in the cell's DNA, and it makes only one copy," he says.
There are significant problems with viral methods, Dr. Wickstrom says. In traditional gene therapy methods, there is a question of how many gene copies may be made in each individual and where in the cell's DNA a copy may go. "The genes could go anywhere in the genome. This may be okay, or they could interact inappropriately with other genes, such as a tumor suppressor gene, knocking out its function and starting a cancer."