Gene therapy with transcription factor decoy oligonucleotides as a potential treatment for cardiovascular diseases.
Cardiovascular diseases including renal diseases are the leading causes of mortality and morbidity in developed countries. Most conventional therapy is inefficient and tends to treat the symptoms rather than the underlying causes of the disorder. Gene therapy based on oligonucleotides (ODN) offers a novel approach for the prevention and treatment of cardiovascular diseases. Gene transfer into somatic cells to interfere with the pathogenesis contributing to cardiovascular disease may provide such a novel approach for better prevention and treatment of cardiovascular disorders. The major development of gene transfer has importantly contributed to intense investigation of the potential of gene therapy in cardiovascular including renal medicine. The amazing advances in molecular biology have provided a dramatic improvement of the technology that is necessary to transfer target genes into somatic cells. Gene transfer methods have been surprisingly improved. In fact, some of them (retroviral vectors, adenoviral vectors or liposome based vectors, etc) have been used in the clinical trials already. Recent progress in molecular biology has provided new techniques to inhibit target gene expression. Especially, application of DNA technology such as an antisense strategy to regulate the transcription of disease-related genes in vivo has important therapeutic potential. Recently, transfection of cis-clement double-stranded ODN (= decoy) has been reported as a new powerful tool in a new class of anti-gene strategies for gene therapy. Transfection of double-stranded ODN corresponding to the cis sequence will result in attenuation of the authentic cis-trans interaction, leading to removal of trans-factors from the endogenous cis-elements with subsequent modulation of gene expression.
Tomita
Naruya
N
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita 565-0871, Japan. tomita@hp-gm.med.osaka-u.ac.jp
Azuma
Haruhito
H
Kaneda
Yasufumi
Y
Ogihara
Toshio
T
Morishita
Ryuichi
R
D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005921:Glomerulonephritis / Q000628:therapy; D006083:Graft Occlusion, Vascular / Q000628:therapy; D006084:Graft Rejection / Q000628:therapy; D006801:Humans; D009203:Myocardial Infarction / Q000628:therapy; D009841:Oligonucleotides / Q000627:therapeutic use*; D014157:Transcription Factors / Q000235:genetics*
D009841:Oligonucleotides; D014157:Transcription Factors