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Testing Boosts Gene Therapies

Closeup of a researcher's face looking through a three-inch glass panel that has several lines and dots etched in it

Assistant Professor James Dahlman holds a microfluidic chip used to fabricate nanoparticles that could be used to deliver therapeutic genes.

By John Toon

Using tiny snippets of DNA as “barcodes,” researchers have developed a new technique for rapidly screening nanoparticles for their ability to selectively deliver therapeutic genes to specific organs of the body. The technique could accelerate the use of gene therapies for such killers as heart disease, cancer, and Parkinson’s disease.

Genetic therapies, such as those made from DNA or RNA, are difficult to deliver into the right cells in the body. For the past 20 years, scientists have been developing nanoparticles made from a broad range of materials and adding compounds such as cholesterol to help carry these therapeutic agents into cells. But the nano­particle carriers must undergo time-consuming testing — first in cell culture, then in animals. With millions of possible formulas, identifying the optimal nanoparticle to target each organ has been challenging.

Using DNA strands just 58 nucleotides long, researchers from Georgia Tech, the University of Florida, and the Massachusetts Institute of Technology (MIT) have developed a new evaluation technique that skips the cell culture testing altogether — and could allow hundreds of different types of nanoparticles to be tested simultaneously in just a handful of animals.

“We want to understand at a very high level what factors affecting nanoparticle delivery are important,” said James Dahlman, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “This new technique not only allows us to understand what factors are important, but also how disease factors affect the process.”

To prepare the nanoparticles for testing, the researchers insert a snippet of DNA that is assigned to each type of nanoparticle. The nanoparticles are injected into an animal model, whose organs are then examined to determine the presence of the barcodes indicating where specific nanoparticles have gone. By using genome sequencing technologies to identify the barcodes, many nanoparticles can be tested simultaneously, each identified by its unique DNA barcode.

The original research was done in the laboratories of Robert Langer and Daniel Anderson at MIT. Supported by the National Institutes of Health, the research was reported in the journal Proceedings of the National Academy of Sciences.

Related: DNA “Barcoding” Allows Rapid Testing of Nanoparticles for Therapeutic Delivery, February 7, 2017

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