Optimization of Antiviral Ribozymes

Many hopes have been placed on ribozymes as agents for fighting viral diseases, especially those caused by RNA viruses. The principle underlying the use of these molecules is their recognition of specific target RNA sequences, and the subsequent cleavage of these by the ribozyme catalytic domain. These events have been extensively documented through the use of in vitro models. However, a number of obstacles have limited the clinical value of ribozymes. An important one is that ribozymes have to compete with the natural folding of the viral RNA target molecules if they are to efficiently access their cognate substrate sequence motif. This chapter provides evidence that ribozymes can, however, be optimized through the addition of an RNA element that promotes their efficient binding to specific structural domains within the target RNA. Ribozyme access to the cleavable phosphodiester bond is thus facilitated, rendering antiviral activity more efficient.