News Section | Immunology
Small doses go a long way
Researchers have found a way of delivering small RNA molecules targeted against the hepatitis B virus at doses that are low enough to allow this new therapeutic approach to be used in people. In the August issue of Nature Biotechnology, David Morrissey and his colleagues incorporate so-called small interfering RNAs (siRNAs) into lipid (fat-like) particles that protect them against digestive enzymes in the blood, thereby increasing their stability when injected into mice and reducing the dose needed for therapeutic effect. These enzymes normally degrade RNA molecules in cells or the circulation.
Previous studies suggested that the amounts of siRNA needed to achieve a therapeutic effect in people far exceed safe levels of exposure to nucleic acids. The work by Morrissey and his colleagues should enable siRNA to be dosed at clinically relevant levels. In their experiments, mice carrying replicating hepatitis B virus were given daily doses of encapsulated siRNAs that specifically targeted the virus. Compared with the plain siRNAs used in previous studies, the encapsulated siRNAs were much more effective at inhibiting viral replication in mice—for up to 7 days after the last dose was given—and worked at much lower doses. What’s more, the encapsulated siRNAs showed persistent activity against hepatitis B virus for up to 6 weeks when given only once a week. These results represent an important step toward the practical implementation of siRNA-based therapeutic strategies.
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Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs David V Morrissey, Jennifer A Lockridge, Lucinda Shaw, Karin Blanchard, Kristi Jensen, Wendy Breen, Kimberly Hartsough, Lynn Machemer, Susan Radka, Vasant Jadhav, Narendra Vaish, Shawn Zinnen, Chandra Vargeese, Keith Bowman, Chris S Shaffer, Lloyd B Jeffs, Adam Judge, Ian MacLachlan & Barry Polisky
Nature Biotechnology, Published online: 24 July 2005 |
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