NEW YORK (Reuters Health) - Using chemically modified short interfering RNA (siRNA), researchers were able to intravenously inject the siRNA into mice and silence an endogenous gene for apolipoprotein B.
Although RNA interference (RNAi) has shown promise as a new therapeutic technique, the main problem has been delivering the siRNA to the gene of interest in vivo. In the present study, Dr. Jurgen Soutschek, from Alnylam Europe AG in Kulmbach, Germany, have come up with one way of solving this problem.
“Our findings demonstrate that RNAi can be used to silence endogenous genes involved in the cause or pathway of human disease with a clinically acceptable formulation and route of administration by systemic delivery,” the investigators note.
As reported in the November 11th issue of Nature, the researchers found that cholesterol conjugation can improve the pharmacologic properties of siRNAs in vitro and in vivo. Using this information, they created siRNAs to silence the apolipoprotein B gene in mice.
After intravenous injection of the siRNAs, the test animals showed a drop in apoB protein levels and in total cholesterol. Further testing showed that such siRNAs could silence the human form of the gene in a transgenic mouse model.
The authors confirmed that the beneficial effects on the lipid profile, were in fact, do to RNAi-mediated mRNA degradation. Moreover, apolipoprotein B mRNA was cleaved exactly where expected.
“To our knowledge, this is the first demonstration of silencing of an endogenous gene in mammals by a mechanism of RNAi-mediated degradation of the target mRNA,” the researchers state.
Source: Nature 2004;432:173-178. [ Google search on this article ]
MeSH Headings:Animal Diseases: Biological Sciences: Biological Therapy: Biology: Disease Models, Animal: Gene Expression Regulation: Genetic Engineering: Genetic Techniques: Genetics: Genetics, Biochemical: Investigative Techniques: Molecular Biology: Therapeutics: Gene Therapy: Gene Silencing: Analytical, Diagnostic and Therapeutic Techniques and Equipment: Biological Sciences: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.