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Putting genes in a pill


Finding new ways to deliver gene therapy without using viruses as carriers is the aim of research by chemist Michael Nantz at UC Davis.

Nantz’s lab engineers lipids, oily molecules that can form a protective complex around DNA, to do the same job as a virus. The lipids protect the DNA and help it get into the target cell. The approach could eventually make gene therapy treatments that are stable enough to take as a pill.

Gene therapy holds the promise of curing diseases such as diabetes, cystic fibrosis or Parkinson’s disease by replacing damaged or missing genes. To do that, a new piece of DNA has to be carried into cells in the right part of the body.

Most approaches have used some kind of genetically modified virus to carry the DNA into the cell. But safety issues have been raised about that approach following the 1999 death of a patient at the University of Pennsylvania and cases of leukemia in two French children being treated for "Bubble baby syndrome."

When the lipid/DNA globule is taken up by a cell, it’s moved to an acid-filled compartment called the endosome. A key step, Nantz said, is to engineer lipids that can get the DNA out of the endosome and into the cell nucleus where most of the genetic material resides.

"What we’re doing is reinventing a virus through chemistry," he said.

In 1998, Nantz helped found a biotech company, Genteric Inc., to develop oral delivery systems for gene therapy. Because cells in the gut turn over quickly, the effect of the gene therapy drops over time. So the treatments can act more like a conventional medicine than a permanent genetic fix.

Andy Fell | EurekAlert!
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