19]Ribozymes as therapeutic agents and tools for gene analysis

Abstract

Publisher Summary This chapter discusses the use of ribozymes as therapeutic agents and tools for gene analysis. Ribozymes are RNA molecules with enzymatic activity. These RNAs can be engineered to base pair with and cleave targeted RNAs, whether they are of cellular or viral origins. Ribozymes have been effectively used in cell cultures against viral targets, endogenous transcripts, and transfected genes. They have also been demonstrated to function effectively in vivo in transgenic animals (mouse and Drosophila ), allowing the generation of phenotypes that are difficult to achieve by conventional genetic approaches. Because of their high target specificity, coupled with the possibility of being delivered either exogenously or endogenously, ribozymes have potential for use in both basic studies and therapeutic applications. There are five catalytic motifs that have been successfully adapted for use in ribozyme applications. These are the group I introns, RNase P, the hammerhead and hairpin motifs, and the self-cleaving domain of the hepatitis delta virus. The chapter presents the catalytic and base pairing domains in a schematic fashion and focuses on the hammerhead ribozyme motif because it has received the most attention from those interested in developing ribozymes as surrogate genetic tools.