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An experimental and potentially powerful way to fight disease, called RNA interference (RNAi), could now be closer to reality, as researchers at MIT and Alnylam, a biotech company based in Cambridge, MA, have addressed a key obstacle to effectively delivering the treatment to targeted cells. The researchers report a method for quickly synthesizing more than a thousand different lipid-like molecules and screening them for their ability to deliver short RNA molecules to cells. They’ve shown that some of these delivery agents are 10 times as effective at delivering RNA than previous methods were.

RNAi, which was first discovered in 1998, has attracted considerable attention as a potential treatment for a wide range of ailments, including cancer, viral infections, genetic diseases, and even heart attacks. Short RNA strands introduced into the cytoplasm of cells block the action of specific genes, while leaving other cellular mechanisms unaffected. This gives scientists a precise tool to stop the expression of specific proteins associated with disease. “You want to shut down just the bad gene–nothing else,” says Robert Langer, a professor of chemical engineering at MIT who led the work developing the new delivery agents. “Most drugs have side effects, in part because of a lack of this type of specificity.” Langer is a member of Alnylam’s scientific advisory board. The work was published this week in Nature Biotechnology.

But since 2001, when RNAi was first demonstrated in mammals, only six RNAi-based therapies have reached clinical trials, and none have yet been approved for use. One big thing holding back RNAi therapy, Langer says, is the lack of an effective delivery mechanism. If RNA is introduced into the bloodstream, the body quickly attacks the RNA and prevents it from reaching the cytoplasm of diseased cells. Progress on finding new delivery agents has been a slow and painstaking process.

The MIT researchers, however, developed a way to make more than a thousand different delivery agents in parallel using a simple, one-step chemical process. And that allowed the team to quickly discover effective delivery molecules, including several that surprised the researchers. “We wouldn’t have necessarily sat down and said, this is a structure that’s going to work,” says Daniel Anderson, a research associate at the David H. Koch Institute for Integrative Cancer Research at MIT. “It was only by making and testing over a thousand that we were able to get to that place.”

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Credit: Daniel Anderson, MIT

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

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