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New nanoparticle delivery device designed for gene therapy

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July 20, 2010

Scientists have created a nanoparticle that can deliver DNA deeply enough into a cell to a...

Scientists have created a nanoparticle that can deliver DNA deeply enough into a cell to allow genetic material to be activated (Image: Michael Strock)

Scientists from Ohio State University (OSU) have created a nanoparticle that can deliver DNA deeply enough into a cell to allow genetic material to be activated. This is a key step in gene therapy, the “reprogramming” of defective genes. Previously, scientists have used deactivated viruses for this task, but have been limited by the body’s immune system attacking those viruses. Nanoparticle delivery is reportedly two-and-a-half to ten times more effective, because it generates much less of an immune response.

The scientists created the nanoparticle, also known as a vector, out of calcium phosphate and a liposome. Calcium phosphate is found in bones and teeth, while liposomes are nanometer-sized bubbles made from lipids - fatty molecules found in cell membranes, that get absorbed by cells. Together, the two materials form a rigid structure that protects its DNA payload from enzymes on the way to a target cell, but that self-destructs once inside that cell.

“Our nanoparticle is a foreign body just like a viral vector is, but it has a self-destructive mechanism so it does not generate a strong response from the immune system,” said Chenguang Zhou, a lead author of the study. “The material we use is also biocompatible. Calcium phosphate is in our bones and the lipids we use are synthetic, but can be biologically degraded. That’s why there is low toxicity.”

Other researchers, Zhou noted, have tried making non-viral vectors out of just liposomes or just calcium phosphate. The liposomes weren’t too effective at releasing their payload into the cell. The calcium phosphate vectors became unstable and expanded, making them too large to penetrate the cell wall, and generating an immune response. By building a vector with a calcium phosphate core inside a liposome, the OSU team overcame the materials’ limitations.

The nanoparticle vectors have been tested on mouse cells, which fluoresced green when DNA carrying the code for green fluorescent protein was successfully delivered into them. The success rate was 24 times higher than when that same DNA had to find its own way in, unprotected, and 10 times higher than when a calcium phosphate-only vector was used.

“We know the particle gets to where it needs to go and what happens to the particle,” Zhou said. “Do we know that the DNA reaches the nucleus? That is something we still need to find out. But because we saw the green fluorescent protein expressed, we think it got to the nucleus or at least as far as the cytoplasm. What’s important is that the protein got inside the cell.”

The research was recently published in the International Journal of Pharmaceutics.

About the Author
Ben Coxworth An experienced freelance writer, videographer and television producer, Ben's interest in all forms of innovation is particularly fanatical when it comes to human-powered transportation, film-making gear, environmentally-friendly technologies and anything that's designed to go underwater. He lives in Edmonton, Alberta, where he spends a lot of time going over the handlebars of his mountain bike, hanging out in off-leash parks, and wishing the Pacific Ocean wasn't so far away.   All articles by Ben Coxworth
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