Scientists discover how to control the shape of nanoparticles that move DNA through the body

(Nanowerk News) Researchers from The Johns Hopkins University and Northwestern University have discovered how to control the shape of nanoparticles that move DNA through the body and have shown that the shapes of these carriers may make a big difference in how well they work in treating cancer and other diseases.
The results of this study, which were published in the journal Advanced Materials ("Plasmid-Templated Shape Control of Condensed DNA–Block Copolymer Nanoparticles"), are also noteworthy because this gene therapy technique does not use a virus to carry DNA into cells. “These nanoparticles could become a safer and more effective delivery vehicle for gene therapy targeting cancer and other illnesses than can be treated with gene medicine,” said Hai-Quan Mao, of Johns Hopkins, who, together with Erik Luijten of Northwestern, led this research.
Dr. Mao and his collaborators have been developing nonviral nanoparticles for gene therapy for a decade. His approach involves encapsulating snippets of therapeutic DNA within protective polymer coatings to form nanoparticles. The particles are designed to deliver their genetic payload only after they have moved through the bloodstream and entered the target cells. Within the cells, the polymer degrades and releases DNA. Using this DNA as a template, the cells can produce functional proteins that combat disease.
A major advance in this work is that Dr. Mao’s team can now create these particles in three shapes, resembling worms, rods, 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,” Dr. Mao explained. These questions were important because the DNA delivery system he envisions may require specific, uniform shapes.
To solve this problem, he sought help from Dr. Luijten, whose expertise lies in computer modeling. “Our computer simulations and theoretical model have provided a mechanistic understanding, identifying what is responsible for this shape change,” Dr. Luijten said. “We now can predict precisely how to choose the nanoparticle components if one wants to obtain a certain shape.”
In their paper, the researchers also wanted to show the importance of particle shapes in delivering gene therapy. Team members conducted animal tests, all using the same particle materials and the same DNA. The only difference was in the shape of the particles: worms, rods, and spheres. “The worm-shaped particles resulted in 1,600 times more gene expression in the liver cells than the other shapes,” Dr. Mao said. “This means that producing nanoparticles in this particular shape could be the more efficient way to deliver gene therapy to these cells.”
Source: National Cancer Institute
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