Therapeutic ribozymes: principles and applications

Ribozymes have progressed from an intriguing subject of scientific study to therapeutic agents for the potential treatment of both acquired and inherited diseases. Clinical trials using ribozymes targeted against HIV, the aetiological agent of AIDS, have recently been initiated. Despite this rapid progression to clinical application, there are many unexplored avenues which still must be examined to improve the intracellular effectiveness of ribozymes. Since ribozymes are RNA molecules which selectively cleave RNA targets via base-pairing interactions, the rules governing nucleic acid hybridisation affect ribozyme function. In addition, knowledge of the cellular mechanisms governing RNA partitioning and stability apply equally to ribozymes as they do to the target RNAs. The successful therapeutic application of ribozymes depends upon increasing our knowledge of RNA metabolism and movement, and applying this knowledge in the design of ribozymes. This review summarises some of the progress and experimental approaches towards achieving these goals as well as surveying experimental testing of potential therapeutic applications. It is becoming increasingly evident that ribozymes can serve the dual function of a tool to elucidate the functional roles of many gene products as well as a therapeutic agent designed to functionally destroy deleterious RNAs.