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Oral Pill May Make Tough-to-Deliver RNAi Drugs Go Down Easy, RXi Says

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One of RXi’s founders, Michael Czech, and a collaborator at the UMass Medical School, Gary Ostroff, believe they have found a “special trick” to make oral delivery work. The researchers have packaged an RNA interference molecule with a beta-glucan particle that disguises it to look like yeast to the body. Once the package goes through the digestive tract, surviving powerful stomach acids, it comes into contact with transporter proteins in the lining of the gut that carry it across the tissue membrane, where it comes into contact with macrophage cells. These cells, which play a role in inflammation, gobble up the cloaked form of the drug, which can then send signals internally to decrease activation of the macrophages.

It’s possible that this technique could be used to decrease the production of a particular inflammatory protein called TNF alpha. That holds big business potential, because some of the world’s best-selling drugs, like Amgen’s etanercept, Johnson & Johnson’s infliximab, and Abbott Laboratories’ adalimumab (Humira) are injectable biotech drugs that block this protein. No one has been able to develop an approved version in an oral pill.

This work still has a lot to prove before outsiders will get too excited. Much work needs to be done before one of these oral RNAi drugs can even make it to clinical trials. Woolf is undeterred. “We have an advantage with delivery of orally available RNAi therapeutics,” he says. “It’s one of the most exciting programs in the field of RNAi.”

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