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The promise of gene therapy has long been held up by the lack of a safe and effective way to insert the desired therapeutic genes into the right cells. To solve that problem, MIT researchers have developed a new polymer for gene therapy that is as effective as viruses, the standard carriers, but it seems to have none of the risks of viral treatments. The researchers have successfully tested a version of the polymer in mice with ovarian cancer, and they believe they can further modify the polymer to target virtually any cell in the body.

Gene therapy works by delivering to a specific group of diseased cells copies of a gene that corrects what ails them. “If you could get it [a gene] where it’s needed, you could treat many diseases,” says the MIT Center for Cancer Research’s Daniel Anderson, one of the leaders of the polymer research group.

The most effective way to get therapeutic genes to the right cells in the body has been by inserting them into viruses, which are then injected into patients. But a series of high-profile setbacks has raised questions about the safety of using viral vectors. Injections of these viruses have caused dangerous, and in several cases deadly, immune reactions in some patients. (See “The Glimmering Promise of Gene Therapy.”) And one class of viruses used for gene therapy can cause leukemia. There are currently many viral gene therapies in clinical trials, but none have been approved by the Food and Drug Administration.

These problems in clinical trials using viruses have spurred researchers to search for synthetic alternatives for delivering gene therapy. “Polymers have been shown safe in people for years,” says Robert Langer, a professor of chemical engineering at MIT and a pioneer in biomaterials research. The polymers under development by the MIT group are relatively inexpensive to manufacture and break down into harmless byproducts in the body. The kind of polymer used as a starting material by the MIT researchers naturally associates with DNA and can succeed in delivering genes into cells.

“They have something comparable [in effectiveness] to viruses,” says David Putnam, assistant professor of chemical and biomolecular engineering at Cornell University. “No one has been able to achieve this.”

The MIT researchers succeeded because they have developed rapid systems for developing and testing large numbers of polymers, says Putnam. “A lot of materials development is a numbers game,” he explains, and the MIT group can design and test new polymers “an order of magnitude faster than everybody else.”

The MIT researchers have previously used an unmodified version of the polymer to selectively deliver a suicide gene to prostate tumors in mice. For their current research, published last week in Advanced Materials, they experimented with making small chemical changes to the ends of the polymers.

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Credit: Jordan Green - MIT

Tagged: Biomedicine, MIT, polymers, virus, genetic therapy

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