Transcription factor decoy oligonucleotide-based therapeutic strategy for renal disease

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Abstract

Renal disease, including slight renal injuries, has come to be seen as one of the risk factors for cardiovascular events. At present, 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 renal diseases. Gene transfer into somatic cells to interfere with the pathogenesis contributing to renal disease may provide such an approach, leading to the better prevention and treatment of renal disease. The major development of gene transfer methods has made an important contribution to an intense investigation of the potential of gene therapy in renal diseases. Amazing advances in molecular biology have provided the dramatic improvement in the technology that is necessary to transfer target genes into somatic cells. Gene transfer methods, especially when mediated by several viral vectors, have improved to a surprising extent. In fact, some (retroviral vectors, adenoviral vectors, or liposome-based vectors, etc.) have already been used in clinical trials. On the other hand, recent progress in molecular biology has provided new techniques to inhibit target gene expression. The transfer of cis-element double-stranded ODN (= decoy) has been reported to be a powerful novel tool in a new class of antigene strategies for gene therapy. The transfer of decoy ODN corresponding to the cis sequence will result in attenuation of the authentic cis-trans interaction, leading to the removal of trans-factors from the endogenous cis-elements with a subsequent modulation of gene expression.

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