Transcription factor decoy oligonucleotide-based therapeutic strategy for renal disease

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.

In vitro DNA-binding profile of transcription factors: methods and new insights

“…In addition, a complete profile of DNA-binding affinity of a TF has promising biomedical applications. For example, DNA sequences with high affinity can be developed as drugs for transcription therapy, such as TF decoys (short duplex oligonucleotide containing DNA-binding site, which can be bound by a TF) (Mann & Dzau 2000, Tomita et al 2007.…”

“…For example, in vitro DBPs of TFs can be used to guide the design and selection of artificial TFs (Gommans et al 2005, Klug 2005, small molecules of TF mimics (Kwon et al 2004, Xiao et al 2007, Block et al 2009, Rodriguez-Martinez et al 2010, Kushal et al 2011, and TF decoys (Penolazzi et al 2007, Tomita et al 2007, which can be developed as drugs for transcription therapy. The in vitro DBPs can also accelerate the creation of precisiontailored DNA therapeutics (Carlson et al 2010).…”

Inhibitory Effect of Nuclear Factor-κB Decoy Oligodeoxynucleotide on Liver Fibrosis Through Regulation of the Epithelial–Mesenchymal Transition

“…To inhibit the binding of transcription factors, a decoy strategy is employed to block transcription factor activity via the use of a synthetic double-stranded oligodeoxynucleotide (ODN), which contains a consensus binding sequence. The decoy ODN strategy has been shown to be an effective approach for suppressing specific gene expression both in vitro and in vivo (Morishita et al, 1998;Tomita et al, 2007). In abdominal aortic aneurysms and renal ischemia-reperfusion, the decoy ODN strategy has been reported as a novel therapeutic application for treating these disorders (Cao et al, 2004;Miyake et al, 2006).…”

Development and Evaluation of Nano‑scale Systems for Targeted Delivery to Treat Liver Fibrosis

“…Decoy ODNs against positive transcription factors can inhibit expression of activated genes and those against negative transcription factors can enhance expression of suppressed genes. 93 After the first artificial 14 mer E2F decoy ODN, targeted to E2F transcription factor (E2F TF), was synthesized by Morishita et al in 1995, 94 other decoy ODNs to target different proteins such as creb, NF-κB, STAT-1, AP-1, have also been found. [95][96][97] Decoy ODNs have been applied to treat cancer, renal diseases, viral diseases or cardiovascular diseases because many of these diseases are due to deregulation of different transcription factors.…”

“…The decoy ODN strategy may not only offer a powerful target-based gene therapy method but also provide a genetic tool to study cellular regulatory processes including upstream transcription regulation and downstream production. 93,98 In 1996, the FDA approved the clinical application of decoy ODN against E2F to treat neointimal hyperplasia in vein bypass grafts. 76 …”