There have been no efforts during this FY to further evaluate the efficacy of multitarget-ribozymes in cells. One of the basic elements that need to be studied in greater detail include the nuclear and cytoplasmic trafficking of mRNAs. The understanding of RNA trafficking will be essential to be able to colocalize the ribozyme with its target RNA and thereby increase efficacy. We hope to be able to continue this project during the next fiscal year. This topic would require major systematic efforts to identify putative cis-acting signals on mRNAs.