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Nano RNA Therapeutics
Lipidlike materials improve delivery of RNA for silencing gene expression

Source: “A combinatorial of lipid-like materials for delivery of RNAi therapeutics”
Daniel G. Anderson et al.
Nature Biotechnology
26: 561-569

Results: By developing new techniques of chemical synthesis, researchers at MIT and Alnylam Pharmaceuticals in Cambridge, MA, were able to quickly make 1,200 different lipidlike molecules that serve as building blocks for nanoscale containers called liposomes. Some of the resulting liposomes proved effective at introducing RNA into a variety of different cells in rodents and primates. The RNA was able to block the action of certain genes and of microRNA, which serves to regulate genes.

Why it matters: Silencing genes with RNA–a technique known as RNA interference, or RNAi–is a potentially powerful therapy for genetic diseases, viral infections, cancer, and even heart attacks, but it’s been difficult to deliver RNA to cells, since the body’s immune system breaks it down quickly. The new delivery agents skirt the body’s defenses.

Access to such a large collection of lipidlike materials will allow scientists to better understand how to design effective delivery nanoparticles. And the new synthesis methods could help researchers find delivery agents that are even more effective, which could increase the chances of success for RNA-based therapies, as well as other drugs.

Methods: The researchers developed a one-step process for making molecules that resemble the lipids typically used for the commercial manu­facture of liposomes. Then they developed ways to screen the ability of liposomes made from these mole­cules to deliver RNA directly to cells in a petri dish and to living tissue in animals.

For in vivo tests, the researchers added cholesterol and an ether called polyethylene glycol to their molecules to help the liposomes avoid the body’s defenses.

Next Steps: Researchers at MIT are sorting through new molecules to find better delivery agents. They are testing their potential for targeting a variety of diseases and for delivering therapeutics other than RNA.

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Credit: J. J. Yang, HP Labs

Tagged: Computing, Materials

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