Ribozymes as a Novel Approach for the Treatment of Human Pancreatic carcinoma

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
).