DNA therapy has long promised to permanently cure a wide variety of diseases, but many obstacles make honoring this promise difficult. Viruses have been the main vector that’s been researched to deliver DNA to target cells, but grappling with potential side effects is a major challenge. Another option is to use simpler, safer nanoparticles to encapsulate DNA.
To that end, researchers from Johns Hopkins and Northwestern universities have developed a way to make DNA containing nanoparticles of different shapes, an advancement that has shown to affect the gene expression of target cells. According to the study, the nanoparticles were created “via condensation of plasmid DNA with a block copolymer of polyethylene glycol and a polycation in solvents of different polarity.” As an example of how the shape of nanoparticles affects the effectiveness of gene therapy, Dr. Hai-Quan Mao of Johns Hopkins, reflecting on an animal cancer study that was conducted, said that “worm-shaped particles resulted in 1,600 times more gene expression in the liver cells than the other shapes.”
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A major advance in this work is that Mao and his colleagues reported that they were able to “tune” these particles in three shapes, resembling rods, worms and spheres, which mimic the shapes and sizes of viral particles. “We could observe these shapes in the lab, but we did not fully understand why they assumed these shapes and how to control the process well,” Mao said. These questions were important because the DNA delivery system he envisions may require specific, uniform shapes.
To solve this problem, Mao sought help about three years ago from colleagues at Northwestern. While Mao works in a traditional wet lab, the Northwestern researchers are experts in conducting similar experiments with powerful computer models.
Erik Luijten, associate professor of materials science and engineering and of applied mathematics at Northwestern’s McCormick School of Engineering and Applied Science and co-corresponding author of the paper, led the computational analysis of the findings to determine why the nanoparticles formed into different shapes.
“Our computer simulations and theoretical model have provided a mechanistic understanding, identifying what is responsible for this shape change,” Luijten said. “We now can predict precisely how to choose the nanoparticle components if one wants to obtain a certain shape.”
Press release: Shape matters in DNA nanoparticle therapy
Abstract in Advanced Materials: Plasmid-Templated Shape Control of Condensed DNA–Block Copolymer Nanoparticles