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A specialized nanoparticle filled with an RNA-based cancer therapy can successfully target human cancer cells and silence the target gene, according to results from an early clinical trial. The research, published today in the journal Nature, is the first to demonstrate this type of tissue targeting and gene-silencing in humans. Researchers haven’t yet revealed the clinical effects of the treatment.

“It’s a very exciting paper,” says Phillip Sharp, an MIT professor who won the 1993 Nobel Prize in medicine for his work on RNA splicing. “It’s a statement that we are in this stage in the field [where we’re] beginning to use these particles to treat people.”

Since the discovery 12 years ago that double-stranded RNA can silence genes in a targeted manner, researchers have hailed the technique, known as RNA interference (RNAi), as a powerful approach to creating new and potent medicines. Indeed, the mechanism garnered its discoverers, Stanford University’s Andrew Fire and Craig Mello of the University of Massachusetts Medical School, the 2006 Nobel Prize in medicine. The trouble is, getting the therapeutic RNA to the right cells has proven to be a sticky challenge. When injected on their own, so-called small interfering RNAs (siRNAs) are quickly filtered out by the kidneys, and researchers have struggled to design particles that carry their contents to target cells with enough specificity, or that don’t cause toxicity or elicit an immune reaction from the body.

So far, a handful of clinical trials have tested the ability of siRNAs delivered directly into the eye or the lung to treat macular degeneration or lung infection caused by respiratory syncytial virus. Because these organs are easily accessible, the therapy was administered directly to the tissue using naked RNA. The new trial, however, is the first to administer the RNA therapy systemically into the body, using specialized particles that protect the RNA while in the bloodstream and target it directly to cancer cells.

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Credit: Swaroop Mishra

Tagged: Biomedicine, cancer, genetics, RNA, RNAi

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