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Better RNA interference, inspired by nature
Date:2/11/2014

yde, or an epoxide. These groups also contribute to the particles' behavior.

Targeted strike

The researchers then tested the particles' ability to shut off the gene for a blood clotting protein called Factor VII, which is produced in the liver by cells called hepatocytes. Measuring Factor VII levels in the bloodstream reveals how effective the siRNA silencing is.

In that initial screen, the most efficient particle contained the amino acid lysine linked to an epoxide, so the researchers created an additional 43 nanoparticles similar to that one, for further testing. The best of these compounds, known as cKK-E12, achieved gene silencing five times more efficiently than that achieved with any previous siRNA delivery vehicle.

In a separate experiment, the researchers delivered siRNA to block a tumor suppressor gene that is expressed in all body tissues. They found that siRNA delivery was very specific to the liver, which should minimize the risk of off-target side effects.

"That's important because we don't want the material to silence all the targets in the human body," Dong says. "If we want to treat patients with liver disease, we only want to silence targets in the liver, not other cell types."

In tests in nonhuman primates, the researchers found that the particles could effectively silence a gene called TTR (transthyretin), which has been implicated in diseases including senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy.

The MIT team is now trying to learn more about how the particles behave and what happens to them once they are injected, in hopes of further improving the particles' performance. They are also working on nanoparticles that target organs other than the liver, which is more challenging because the liver is a natural destination for foreign material filtered out of the blood.


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Contact: Sarah McDonnell
s_mcd@mit.edu
617-253-8923
Massachusetts Institute of Technology
Source:Eurekalert

Page: 1 2 3

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