A nuclease-resistant protein kinase C alpha ribozyme blocks glioma cell growth.

We investigated the cleavage activity, stability, and efficacy of 2'-amino pyrimidine modified ribozymes on malignant glioma growth. A synthetic protein kinase C alpha (PKC alpha) ribozyme with complete pyrimidine nucleotide substitution retained a comparable cleavage activity compared with the unmodified ribozyme. The half-life of the modified ribozyme in serum was increased 14,000-fold compared with the unmodified version. The PKC alpha modified ribozyme inhibited glioma cell growth in vitro as a result of the inhibition of PKC alpha gene expression. A single injection of cationic liposome ribozyme complexes into glioma tumors inhibited tumor growth, demonstrating both the efficacy of the ribozyme and a major role of PKC alpha in tumor growth.