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Shape Matters in DNA Nanoparticle Therapy

October 12, 2012

This illustration depicts DNA molecules (light green), packaged into nanoparticles by using a polymer with two different segments. One segment (teal) carries a positive charge that binds it to the DNA, and the other (brown) forms a protective coating on the particle surface. By adjusting the solvent surrounding these molecules, the Johns Hopkins and Northwestern researchers were able to control the shape of the nanoparticles.

Johns Hopkins researchers, working with colleagues from Northwestern University, have found a way to control the shape of nanoparticles that move DNA through the body, and they have discovered that shape may impact the effectiveness of these particles in treating disease.

The study, published in the Oct. 12 online edition of Advanced Materials, is noteworthy because this gene therapy technique does not use a virus to carry DNA into cells, an approach that has posed its own health risks. Instead, it uses nanoparticles that mimic the shape of virus particles.

“These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer, and other illnesses,” says Hai-Quan Mao, an associate professor of materials science and engineering at the Whiting School of Engineering, and co-corresponding author of the article.

Mao and his colleagues were able to “tune” the particles into three shapes, resembling rods, worms, and spheres, which mimic the shapes and sizes of viral particles. Northwestern researchers led computational analysis to determine why the nanoparticles formed these different shapes. “The worm-shaped particles resulted in 1,600 times more gene expresssion in the liver cells than the other shapes. This means that producing nanoparticles in this particular shape could be the more efficient way to deliver gene therapy to these cells,” Mao says.

Lead authors of paper were Xuan Jian, a doctoral student in Mao’s lab, and Wei Qu, a graduate student in Erik Luijten’s research group at Northwestern.

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