Design of a ribozyme to therapeutically increase the DNA damage in a solid tumor. Ribozymes are catalytic RNA molecules which can be targeted to cleave a specific mRNA and hence decrease the level of that protein. The base excision repair pathway then removes the U from DNA, which introduces DNA strand breaks. The final result is the fragmentation of DNA in replicating cells. Four ribozymes have been designed that cleave the dUTPase RNA in vitro.
Work is underway to characterize cell lines expressing the ribozymes.
It has also been suggested that damage to the mitochondrial DNA may play a particularly important role in aging. We have designed an antisense RNA to down-regulate the mitochondrial dUTPase in human cells. We plan to study the effect of accumulation of mitochondrial DNA damage on the growth, morphology and gene expression of cultured primary cells. Repair of ionizing radiation DNA damage in cells. The clusters of lesions consist of oxidized base damages, single strand breaks and sites of base loss.