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Jumping gene could provide non-viral alternative for gene therapy

ecular biologist, at the University of Hawaii and a corresponding author. "But by comparing different transposons, we showed Sleeping Beauty is far inferior to piggyBac."

Scientists have used viruses as a gene delivery mechanism for more than 20 years because of their adeptness at getting inside cells and inserting themselves in DNA. But efficiency comes at a price. Gene therapy trials have been halted because of major complications, including deaths. As examples, one patient died because of his immune response to an adenovirus and three children in another study developed leukemia because the virus inserted itself upstream of a cancer-causing gene.

"With viruses, you don't have control," says Dr. Kaminski. "People have tried to modify viruses for site-specific integration and have not been very successful. Once they get into the cell, they can insert wherever they want."

Dr. Kaminski's previous work, published in 2002 in The FASEB Journal, hypothesized that the integration site for transposons can be selected. "Typically, viruses and transposons will integrate anywhere along the genome," he says. "If they integrate anywhere, it can obviously cause harm. If we can target the integration, be able to insert the gene at a safe spot in the genome, that would be beneficial." He confirmed that targeting integration is possible in a paper he co-authored in 2005 also in The FASEB Journal. "We can do it in insects," says Dr. Moisyadi. "I think it's a short step to take it to a targeting mechanism we can use in humans."

Another clear benefit is that transposons are cheaper to produce and probably safer than viruses. For example, retroviruses use RNA to make DNA, an error-prone process that must occur before integration, Dr. Kaminski says. Also, viruses can't carry larger genes, such as the dystrophin gene, which could help correct muscular dystrophy. On the other hand, unlike retroviruses, transposons have to be coated with lipid to slip
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Source:Medical College of Georgia


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