A nuclease-resistant protein kinase Cα ribozyme blocks glioma cell growth

被引：70

作者：

Sioud, M ^{[1
]}

Sorensen, DR

机构：

[1] Norwegian Radium Hosp, Dept Immunol, Canc Res Inst, N-0310 Oslo, Norway

[2] Natl Hosp Norway, Anim Unit, N-0027 Oslo, Norway

来源：

NATURE BIOTECHNOLOGY | 1998年 / 16卷 / 06期

关键词：

gene expression; antisense; 2 '-amino pyrimidines;

D O I：

10.1038/nbt0698-556

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：556 / 561

页数：6

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