Development of ribozymes for gene therapy

Abstract

Ribozymes are a class of RNA molecules that can perform catalytically in the absence of protein. Specifically, they can hybridize to and cleave target RNA molecules independent of cellular proteins. The cleaved target RNA can not be translated thereby preventing synthesis of a specific protein. The therapeutic application is to target the ribozyme to the mRNA of a key protein or proteins involved in maintaining a disease state resulting in a cure. The ribozymes can be chemically synthesized and delivered to cells or they can be expressed from an expression vector following either permanent or transient transfection. Therapeutic applications of ribozymes have been in the areas of AIDS and cancer. The following article describes the ribozymes in more detail with respect to optimizing the design to obtain the maximal cleavage rate, identifying cleavage sites within the target RNA and delivering the ribozymes to cells of interest both in vitro and in vivo.