Slowly does it


By Nell Boyce in Washington DC TISSUE engineers in the US have developed biodegradable “scaffolding” for gene therapy that slowly releases DNA in the body, allowing surrounding cells to take it up and make therapeutic proteins. This approach seems to be far more successful at persuading cells to take up DNA than conventional gene injections. The new technique could make it easier to grow replacement organs, and eventually doctors could use it to help their patients grow new tissue. A polymer matrix surgically implanted in a joint could be filled with DNA to stimulate regrowth of cartilage, for example. In the 1980s, researchers developed the first biodegradable scaffolding, which they seeded with cells that grew and created new tissue. They used collagen or polymers made of lactic and glycolic acid to create either rigid mesh or sponge-like constructions that could be bathed with fluids in an incubator and seeded with cells. It was simple to coat these scaffolds with growth hormones, but getting the proteins inside them proved more of a challenge because the polymer—and the organic solvents used to make it—sometimes destroyed the proteins. So a group led by David Mooney at the University of Michigan in Ann Arbor decided to avoid using proteins and insert the DNA into the scaffold instead, hoping that the cells would take up the genetic information and make their own proteins. Mooney’s team chose a scaffold made of polylactide coglycolide, to which they added a mixture of salt and small loops of DNA, called plasmids. To trap the DNA they used pressurised carbon dioxide to create tiny bubbles in the polymer. DNA and salt diffused into the bubbles. The salt was then washed away, leaving the DNA behind. To see how well cells would take up genes released by the slowly degrading polymer, they placed spongy discs of the scaffold containing a marker gene under the skin of rats. When they stained cells from around the scaffold, they found a surprisingly large number of them had taken up the marker gene. When a milligram of DNA plasmids are injected, typically only a hundred to a thousand cells will take them up. The slow-release DNA seemed to get into around 100 000 to 1 000 000 cells. Encouraged, the group engineered another polymer disc to carry a gene for a growth factor that promotes wound healing and blood-vessel growth, called platelet-derived growth factor. Sure enough, the rats’ wounds healed better and they grew more blood vessels than controls ( Nature Biotechnology, vol 17, p 551). Injecting the same amount of genes into the wounded area did not significantly affect tissue growth, and Lonnie Shea of the Michigan team says that repeated exposure to a gene as the polymer breaks down simply gives the cells more opportunities to take it up. The team’s polymer scaffolds can slowly release DNA plasmids for up to a month. Shea says of his technique:
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