A jumping gene first identified in a cabbage-eating moth may one day provide a safer, target-specific alternative to viruses for gene therapy, researchers say.

They compared the ability of the four best-characterized jumping genes, or transposons, to insert themselves into a cell's DNA and produce a desired change, such as making the cell resistant to damage from radiation therapy.

They found the piggyBac transposon was five to 10 times better than the other circular pieces of DNA at making a home and a difference in several mammalian cell lines, including three human ones.

"If we want to add a therapeutic gene, we can put it within the transposon and use it to deliver the gene into the cell," says Dr. Joseph M. Kaminski, radiation oncologist at the Medical College of Georgia Cancer Center and a corresponding author on research published the week of Sept. 25 in the online Proceedings of the National Academy of Sciences Early Edition. "You can use these wherever retroviruses have been used."

In addition to piggyBac, researchers looked at what was believed to be the most efficient transposon in mammalian cells, hyperactive Sleeping Beauty, first found "asleep" in fish. They also looked at Tol2, another fish transposon, and Mos1, found in insects.

The piggyBac transposon, which has close relatives in the human genome, is widely used to genetically modify insects. Sleeping Beauty has been used to correct hereditary diseases, including hemophilia, in a mouse model.

For this study, researchers used transposons to deliver an antibiotic-resistant gene. "It's a way of screening and seeing which transposon is better," Dr. Kaminski says. They found that while piggyBac might not work as efficiently as a virus, it put Sleeping Beauty to shame when it came to making cells antibiotic-resistant.

"Sleeping Beauty has captured the field as far as transposons to be used in mammals," says Dr. Stefan Moisyadi,
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
25-Sep-2006