| Abstrakt: |
Current advances in the understanding of the genetic mechanisms of carcinogenesis and manipulation of gene expression have introduced gene therapy as a new strategy for cancer therapeutics. Recently, gene modulation using specific oligonucleotides have been developed and defined as an effective strategy for suppressing the function of genes (1-4). The types of oligonucleotides used to modulate specific gene expression include triplex DNA, antisense DNA/RNA and ribozymes (catalytic RNAs; for a review seeref. 1). Antisense oligonucleotides are capable of altering the translation of mRNA and thus inhibit the transfer of information from the gene to the protein. Antisense-mediated gene modulation has been shown to be effective for gene therapy (5-7). In contrast, ribozymes have been characterized as RNA molecules having site-specific catalytic activity (8,9). Trans-acting ribozyme molecules, such as "hammerhead" and "hairpin" ribozymes, possess a catalytic core and two flanking sequences which bind specifically to its target mRNA. Ribozymes are also occasionally defined as "partial" antisense molecules. However, compared to the classical an&sense-mediated gene modulation, ribozyme strategies have a few advantages due to their site-specific cleavage activity and catalytic potential (2,10). In recent years, researchers have described the efficacy of ribozymes against various oncogenes, such as ras, c-fos, and bcr-abl (11), the MDR-1 drug resistance gene (12,13), and the human immunodeficiency virus type 1 (10,14,15). Our Studies have previously demonstrated that anti-oncogene ribozymes effectively suppress the expression of targeted genes and result in the reversal of the malignant phenotype in human cancer cells (16-24). [ABSTRACT FROM AUTHOR] |
