Tomita Naruya, Kashihara Naoki, Morishita Ryuichi
Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan.
Clin Exp Nephrol. 2007 Mar;11(1):7-17. doi: 10.1007/s10157-007-0459-6. Epub 2007 Mar 28.
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.
肾脏疾病，包括轻微的肾损伤，已被视为心血管事件的危险因素之一。目前，大多数传统疗法效率低下，且往往只是治标而非治本。基于寡核苷酸（ODN）的基因疗法为肾脏疾病的预防和治疗提供了一种新方法。将基因导入体细胞以干扰导致肾脏疾病的发病机制可能提供这样一种方法，从而更好地预防和治疗肾脏疾病。基因转移方法的重大发展为深入研究基因疗法在肾脏疾病中的潜力做出了重要贡献。分子生物学的惊人进展使得将靶基因导入体细胞所需的技术有了显著改进。基因转移方法，尤其是由几种病毒载体介导时，已经有了惊人的改进。事实上，一些（逆转录病毒载体、腺病毒载体或基于脂质体的载体等）已经用于临床试验。另一方面，分子生物学的最新进展提供了抑制靶基因表达的新技术。据报道，顺式元件双链ODN（=诱饵）的转移是基因疗法中一类新的抗原策略中的一种强大的新工具。对应于顺式序列的诱饵ODN的转移将导致真实的顺式-反式相互作用减弱，从而使反式因子从内源性顺式元件中去除，进而调节基因表达。
