Anti-oncogene hammerhead ribozymes (RNA enzymes) specifically inhibit oncogens in a mice model system.

胰腺癌是人类致死性癌症之一，目前迫切需要开发新的治疗策略。K-ras基因的点突变在人类胰腺癌中发病率很高。这些改变可以作为特定核酶介导的恶性表型逆转的潜在靶点。我们已经在Capan-1人胰腺癌细胞系中证明了锤头核酶对活化的K-ras基因密码子12的有效性。为了将这一策略应用于治疗，我们设计了一种重组腺病毒，编码抗k -ras核酶的基因盒。通过在小鼠模型系统中使用该重组腺病毒，可以实现K- ras基因突变的人胰腺肿瘤恶性表型的有效逆转。腺病毒介导的高效抗癌基因核酶递送可能成为一种重要的人类恶性肿瘤基因治疗策略。

Pancreatic cancer is one on lethal human cancers, and development of its new therapeutic strategy is eagerly required today. Point mutation in the K-ras gene is observed at a high incidence in human pancreatic carcinomas. These alterations can be used as potential targets for specific ribozyme-mediated reversal of the malignant phenotype. We have demonstrated the efficacy of a hammerhead ribozyme directed against codon 12 of the activated K-ras gene in a Capan-1 human pancreatic carcinoma cell line. To develop this strategy into a therapeutic application, we designed a recombinant adenovirus encoding a gene cassette for the anti-K-ras ribozyme. By using this recombinant adenovirus in a mice model system, it was possible to accomplish efficient reversion of the malignant phenotype in human pancreatic tumors with K- ras gene mutation. The high efficiency adenoviral-mediated delivery of anti-oncogene ribozyme could emerge as a significant gene therapy strategy against human malignancies.