Suppression of apoptosis in the liver by systemic and local delivery of small-interfering RNAs.
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.
Zender
Lars
L
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Kubicka
Stefan
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D023281:Genomics / Q000379:methods; D006509:Hepatitis B / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D051379:Mice; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering