SUPPRESSION OF THE NEOPLASTIC PHENOTYPE IN-VIVO BY AN ANTI-RAS RIBOZYME

In this study, the efficacy of an anti-ras ribozyme in reversing the n eoplastic phenotype was investigated. Murine NIH3T3 cells were transfe cted with cellular DNA from the FEMX-I human melanoma cell line expres sing the activated H-ras gene. The transformed cells displayed the neo plastic phenotype in vitro and were tumorigenic in nude mice in vivo. When the transformants were transfected by a ribozyme designed to clea ve only activated H-ras RNA, the transformed phenotype was abrogated. In contrast, expression of a mutant ribozyme, essentially acting only as antisense, into the transformed cells resulted in less dramatic cha nges in cell growth and tumorigenicity. These results reinforce the po tential role of anti-oncogene ribozymes as suppressors of neoplastic g rowth, with possible implications for gene therapy.