OPTIMIZING RIBOZYMES FOR SOMATIC-CELL GENE-THERAPY

Therapeutic ribozymes are created through a multistep process that req uires trial and error. There are few established rules governing riboz yme design, but guidelines are emerging, It is not yet known whether h ammerheads and hairpins, the two ribozymes most widely studied as pote ntial gene therapy agents, have the inherent capability to ablate sing le genes, Their capacity for specificity and selectivity remains to be explored through rigorous experimentation. These experiments require a battery of control molecules, the characteristics of which are outli ned here. Methods for completing the steps in the ribozyme development process, from the selection of a target gene to the quantitation of R NA levels, are also presented and discussed.