Abstract
We investigated the cleavage activity, stability, and efficacy of 2′-amino pyrimidine modified ribozymes on malignant glioma growth. A synthetic protein kinase Cα (PKCα) 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 PKCα modified ribozyme inhibited glioma cell growth in vitro as a result of the inhibition of PKCα 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 PKCα in tumor growth.
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Sioud, M., Sørensen, D. A nuclease-resistant protein kinase Cα ribozyme blocks glioma cell growth. Nat Biotechnol 16, 556–561 (1998). https://doi.org/10.1038/nbt0698-556
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DOI: https://doi.org/10.1038/nbt0698-556
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