Abstract
Gene therapy is emerging as a potential strategy for the treatment of cardiovascular disease such as restenosis after angioplasty, vascular bypass graft occlusion, transplant coronary vasculopathy, for which no known effective therapy exists. One strategy for combating disease processes has been to target to the transcriptional process. Two approaches have been used to accomplish this. One is the use of antisense that is complimentary to the mRNA of interest. The second approach is the use of ribozymes, a unique class of RNA molecules that not only store information but also process catalytic activity. Ribozymes are known to catalytically cleave specific target RNA leading to degradation, whereas antisense inhibit translation by binding to mRNA sequences on a stoicheometric basis. Theoretically, ribozymes are more effective to inhibit target gene expression. Especially, the application of DNA technology such as antisense strategy to regulate the transcription of disease-related genes in vivo has i mportant therapeutic potential. More recently, transfection of cis-element double stranded (ds) oligodeoxynucleotides (ODN) (= decoy) as a powerful tool in a new class of anti-gene strategies for gene therapy has been reported. Transfection of ds ODN corresponding to cis sequence will result in the attenuation of authentic cis-trans interaction, leading to the removal of trans-factors from the endogenous cis-elements with subsequent modulation of gene expression. This decoy strategy is not only a novel strategy for gene therapy as an anti-gene strategy, but also a powerful tool for the study of endogenous gene regulation in vivo as well as in vitro. In this review, we have focused on the future potential of oligonucleotide (antisense, decoy and ribozyme)-based gene therapy for the treatment of cardiovascular disease
Keywords: Antisene, Decoy, Antigene, Novel cardiovascular Drug, Plasminogen, VCAM, ELAM, ICAM, Hypertension, Angioplasty
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