The tight network of endothelial cells of brain capillaries have, until now, kept therapeutic molecules, such as small interfering RNAs (siRNAs), from crossing from the blood into the brain. Such molecules could potentially silence targeted genes expressed in neurologic disorders. N. Manjunath Swamy from Harvard University Medical School and colleagues synthesized a peptide derived from rabies virus glycoprotein (RVG) and showed that the 29-amino-acid peptide bound specifically to acetylcholine receptors expressed in the brain. 1 When they gave the RVG peptide (complexed with an antiviral) intravenously to mice, they silenced specific genes in the brain that were involved in an otherwise fatal form of viral encephalitis. Repeated administration of the peptide-siRNA complex did not trigger inflammatory cytokines or antipeptide antibodies.
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Transvascular siRNA Delivery
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