Antibody Targeted siRNA Delivery.
Methods in molecular biology, January 2011
Masoud M. Toloue, Lance P. Ford
It is very clear that RNA interference (RNAi) is a potent and versatile tool for gene silencing. One of the hurdles to making siRNA/miRNA a human therapeutic includes effective in vivo delivery and being able to deliver drugs to target cells only. The commercial success of in vivo applications of RNAi hinges on the development of new delivery methods. Our strategy involves the use of antibody-based delivery agents to target and deliver siRNA into specific cell types. We have developed antibody-based agents for directed delivery into cultured cells and animal disease models. Using antibodies against various cell surface receptors, modified siRNAs are attached to antibody complexes using RNA carrier proteins. The complex can then be intravenously administered to in vivo models and taken up by specific cells via receptor-mediated endocytosis. The labile structure of the linking agents enables release of siRNA molecules post internalization. Using this targeting strategy, we have developed a method that allows any commercially available or recombinant antibody to be conjugated to siRNA for delivery purposes.
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