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The development of efficient methods for manipulation of cell-specific gene expression in vivo is of great value for gaining new insights into complex biological systems, and for advancing gene therapy for human diseases. Transcript-specific downregulation of RNA levels and activity using antisense RNA techniques represents a promising approach toward this end. However, with a few exceptions, the use of antisense RNA in vivo has met with limited success. One major obstacle is the need to maintain relatively high intracellular levels of the antisense RNA, which interacts stoichiometrically with the target transcript. The discovery of ribozymes opened the way for incorporating catalytic RNA elements into antisense RNA. This allows one antisense RNA molecule to inactivate multiple target RNA molecules, thus reducing the constraint for overexpression of the antisense RNA in the cells.
