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RNA interference (RNAi) is a widely embraced technology for silencing genes, preventing them from making the messenger RNA needed to make proteins. Despite its implications for medicine, RNAi has largely been confined to research applications. In January, Judy Lieberman, MD, PhD, of the Program in Cellular and Molecular Medicine and the Immune Disease Institute at Children's Hospital Boston (PCMM/IDI), was the first to show that RNAi could be the basis for therapy, using an RNAi-based vaginal cream to block sexual transmission of herpes virus in mice by disabling certain genes. However, the problem of how to give RNAi systemically, while targeting specific tissues in the body, remains unsolved.
Now, in work that began in collaboration with Lieberman, Motomu Shimaoka, MD, PhD, of PCMM/IDI has found a way to get RNAi to white blood cells, potentially treating a wide range of diseases involving the immune system. Their strategy makes use of integrins, receptor molecules on cells that act as a kind of glue, enabling cells to adhere to each other and their surrounding matrix.
By targeting an integrin called beta7, Shimaoka and colleagues were able to deliver short interfering RNAs (siRNAs) to white blood cells involved in intestinal inflammation (colitis). The siRNA carrier was a specially designed nanoparticle, guided to the integrin by an attached monoclonal antibody. When injected intravenously into mice with colitis, the particles entered immune cells in the inflamed gut via beta7 integrin, silenced an inflammatory gene, suppressed intestinal inflammation and reversed the disease.
This study, published last year in Science, provided proof-of-principle that this technique could be used to treat inflammatory, autoimmune and allergic diseases involving white blood cells. But Shimaoka sees additional applications. He is at work on developing integrin-based RNAi approaches to combat HIV infection and for blood cancers such as multiple myeloma that are difficult to reach with conventional approaches.
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