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Brain tumor cells penetrated by tiny, degradable particles carrying genetic instructions
Date:4/29/2014

ng their effectiveness. "Nanoparticles that remain stable for such a long time allow us to make up formulations well in advance and in large batches," says Stephany Tzeng, Ph.D., a member of Green's team. "This makes them easy to use consistently in experiments and surgeries; we add water to the particles, and they're good to go."

In a related study, published online on March 27 in the same journal, Green's group also showed that a different particle formulation could effectively carry and deliver so-called siRNAs to brain cancer cells. siRNAs are very small molecules that carry genetic information to cells, but unlike DNA that can turn genes on, siRNA interferes with the production of particular proteins and can turn cancer genes off.

Green explains that siRNAs must be encapsulated in particles that are different from those used to carry DNA because siRNAs are about 250 times smaller than the DNA molecules usually used for gene therapy. "siRNAs are also much stiffer than DNA, and they don't have to enter the cell nucleus because they do their work outside it, in the cytoplasm," he says.

An initial library of 15 biodegradable particle formulations was tested for their ability to carry siRNAs into human glioblastoma cells that were genetically engineered to make green fluorescent protein (GFP). The siRNAs added to the particles contained the GFP code, so successfully targeted cells would stop glowing green.

By tweaking the chemical properties of the particles, the team was able to find a composition that decreased GFP's glow in the human brain cancer cells by 91 percent. To test the ability of the particles to deliver death-inducing siRNAs, the team loaded the particles with a mixture of siRNA codes designed to prevent important proteins from being made. They then added these particles to brain cancer cells and to non-cancerous brain cells growing in the laboratory.

As in their mouse study, the siRNA was more effective i
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Contact: Catherine Kolf
ckolf@jhmi.edu
443-287-2251
Johns Hopkins Medicine
Source:Eurekalert  

Page: 1 2 3 4

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