SpringerProtocols: Abstract: Suppression of Apoptosis in the Liver by Systemic and Local Delivery of Small-Interfering RNAs

Suppression of Apoptosis in the Liver by Systemic and Local Delivery of Small-Interfering RNAs

By: Lars Zender², Stefan Kubicka³

Abstract

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RNA interference (RNAi) is a sequence-specific gene-silencing mechanism triggered by double-stranded RNA. RNAi was shown to allow transient or stable knockdown of gene expression in a broad range of species and has been used successfully for functional genomic screens in mammalian cells and Caenorhabditis elegans. Standard therapeutic use of RNAi in clinical settings in humans has been hampered by the lack of effective methods to deliver the small-interfering RNAs (siRNAs) or short-hairpin RNA expression vectors into the diseased organs. In mice, systemic delivery of siRNAs by hydrodynamic intravascular injection leads to highly efficient uptake of siRNAs into the liver. Several groups demonstrated therapeutic use of RNAi in mouse models of acute liver failure or hepatitis B virus replication. This chapter will focus on the technical background of hydrodynamic and portal vein delivery techniques in mice and will give practical guidance for using these techniques for siRNA delivery into the liver.

Affiliation(s): (2) Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
(3) Department of Gastroenterogy, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany

Book Title: Target Discovery and Validation Reviews and Protocols: Volume 2: Emerging Molecular Targets and Treatment Options

Series: Methods in Molecular Biology | Volume: 361 | Pub. Date: Feb-05-2007 | Page Range: 217-226 | DOI: 10.1385/1-59745-208-4:217

Subject: Pharmacology/Toxicology

Key Words: siRNA - RNA interference - hydrodynamic intravascular injection - apoptosis - acute liver failure

References

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