[49] Ribozymes in treatment of inherited retinal disease

Naturally occurring ribozymes fall into three broad classes: (1) RNase P, (2) self-splicing introns, and (3) self-cleaving viral agents. RNase P is required for tRNA processing. Self-splicing introns include the group I and II introns of bacteria, mitochondria, and chloroplasts. Self-cleaving agents include hepatitis delta virus and components of plant viroids that sever the RNA genome as part of a rolling-circle mode of replication. The catalytic properties and greater specificity of ribozymes give them potential advantage over antisense RNA. Two kinds of ribozyme have been widely employed: hairpins and hammerheads. Both were originally derived from the satellite RNA of tobacco ringspot virus, and each derives its name from its schematic secondary structure. Both hammerheads and hairpins were successfully tested for gene therapy of rat models of autosomal dominant retinitis pigmentosa (ADRP). This chapter presents methods tested on retinal targets. The strategy has been to express ribozymes in a cell type-specific manner, using the promoter from the rod opsin gene.