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March 27, 2008

Scientists Uncover New Route that siRNAs Take in Angiogenesis Suppression

  • Researchers report that they have made a discovery that challenges the view that siRNA’s therapeutic effects are imparted solely through RNAi. The team was studing siRNA targeting involved in angiogenesis in patients with blinding choroidal neovascularization from age-related macular degeneration (AMD).

    “siRNAs are used in every area of biomedical research and are thought to be exquisitely specific in targeting a single gene,” says Jayakrishna Ambati, M.D., a University of Kentucky researcher and the paper’s senior author. “My lab made the surprising discovery that siRNAs including those in clinical trials do not enter cells or trigger RNAi. Rather, we found that they generically, regardless of their sequence or target, bind a receptor known as TLR3 on cell surfaces and block blood vessel growth in the eye, skin, and a variety of other organs.”

    Dr. Ambati’s team also showed that people with a mutation in the TLR3 receptor are resistant to the generic effects of siRNAs.

    Blocking blood vessel growth is beneficial in a variety of diseases. Prime examples include wet AMD and cancer. Blocking blood vessel growth by administering siRNA intravenously, however,  could be detrimental if it impacts other organs.

    The research was conducted by investigators at The University of Kentucky, The University of North Carolina at Chapel Hill, Nagoya City University Medical School, Oregon Health and Science University, University of Utah School of Medicine, University of Pennsylvania School of Medicine, University of Illinois at Chicago College of Dentistry, and University of North Carolina at Greensboro.

    The paper was published online on March 26 in Nature.