A nuclease-resistant protein kinase Cα ribozyme blocks glioma cell growth
- 1 June 1998
- journal article
- Published by Springer Nature in Nature Biotechnology
- Vol. 16 (6) , 556-561
- https://doi.org/10.1038/nbt0698-556
Abstract
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.Keywords
This publication has 30 references indexed in Scilit:
- Efficient hammerhead ribozyme and antisense RNA targeting in a slow ribosome Escherichia colimutantNature Biotechnology, 1997
- Isolation of a nuclease-resistant decoy RNA that selectively blocks autoantibody binding to insulin receptors on human lymphocytes.The Journal of Experimental Medicine, 1996
- Enhancement of Hammerhead Ribozyme Catalysis by Glyceraldehyde-3-phosphate DehydrogenaseJournal of Molecular Biology, 1996
- Chemical Modification of Hammerhead RibozymesJournal of Biological Chemistry, 1995
- Controlled, targeted, intracellular expression of ribozymes: Progress and problemsTrends in Biotechnology, 1995
- Interaction Between Tumour Necrosis Factor α Ribozyme and Cellular Proteins: Involvement in Ribozyme Stability and ActivityJournal of Molecular Biology, 1994
- Brain Tumor Working Group Report on the 9th International Conference on Brain Tumor Research and TherapyJournal of Neuro-Oncology, 1993
- Intracellular Signaling by Hydrolysis of Phospholipids and Activation of Protein Kinase CScience, 1992
- Ribozymes as Potential Anti-HIV-1 Therapeutic AgentsScience, 1990
- The Chemistry of Self-Splicing RNA and RNA EnzymesScience, 1987