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The researchers began with the observation that certain lipid molecules had properties that made them attractive for delivering RNA. Since these were difficult to synthesize, the team turned to amine-based molecules that were similar in many ways, but easier to make. By combining amino molecules with alkyl-akrylates and alkyl-acrylamides, the researchers were able to make more than a thousand different lipid-like molecules. These molecules have properties that cause them to assemble into nanoscale capsules called liposomes, which can encapsulate RNA molecules. The researchers then tested the ability of the liposomes to deliver RNA to the cytoplasm of cells by using a screening method they developed that involves blocking the bioluminescence in genetically engineered cells.

In tests on mice, the best of these delivery agents were 10 times as effective at delivering RNA to treat a respiratory ailment, compared with existing methods that deliver the RNA directly to the lungs without it being encapsulated. The researchers also demonstrated that the agents worked for delivering RNA through the bloodstream to the liver and various tissues. What’s more, initial tests in primates showed promising results. Perhaps most important, Anderson says, is the fact that the team can make several variants of a delivery agent, which could make it more likely that one of them will survive all the stages of clinical trials.

The researchers are working with Alnylam, which will be moving the delivery agents toward clinical trials. They’re also continuing to sort through new variants of the molecules to find ones that work better, and they’re testing the effectiveness of the delivery agents for targeting different diseases and for delivering different therapeutics in addition to RNA.

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Credit: Daniel Anderson, MIT

Tagged: Biomedicine, cancer, nanotechnology, drug delivery, RNAi, therapeutics

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