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One of the reasons gene therapy has faltered so far is that it’s hard to get the right genes into cell nuclei safely. Genetically modified viruses are a common but less-than-ideal vehicle for the genes because the viruses can cause a fatal immune response. Looking for a way to deliver the genetic goods harmlessly and efficiently, cancer researcher Gayle Woloschak of Northwestern University Medical School and researchers at Argonne National Laboratory are turning to nanocrystals-particles a few billionths of a meter in diameter.

The tiny particles act as “scaffolding” for the genetic material and make it possible to attach other molecules, such as peptides, that can help guide the complex directly to a cell’s nucleus. In initial experiments, Woloschak and her coworkers used a small electrical stimulus to make the cell wall semipermeable, allowing the nanocrystals, which are only slightly wider than DNA, to slip through. Currently, the scientists are working on adding a navigational peptide to the scaffolding.

To make the crystals, Woloschak and her colleagues used titanium dioxide, a material that shouldn’t provoke the immune system. Nanocrystals are attractive also because they can bear multiple genes, a property that could simplify therapy for diseases caused by several malfunctioning genes, Woloschak says. The nanocrystals may also provide a way to knock out unwanted genetic material, she adds. The researchers would attach to the nanoparticle a short stretch of DNA that matches a defective gene sequence; once bound with the unwanted genetic material in the cell, the nanoparticle could be broken apart by light or x-rays, thereby snipping out the problematic DNA.

Although Woloschak says the group’s work is at least two years away from animal testing, nanoparticles’ potential is definitely beginning to crystallize. “The hope is that nanoparticles will be able to incorporate some of the useful features of a viral vector, like the localization peptides, without the concern that they’ll cause a negative immune reaction,” says Daniel Feldheim, a North Carolina State University chemist who is developing gold nanoparticles that may also be enlisted in gene therapy efforts.

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