Gene therapy with transcription factor decoy oligonucleotides as a potential treatment for cardiovascular diseases.
Gene therapy with transcription factor decoy oligonucleotides as a potential treatment for cardiovascular diseases.
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DOI：
10.2174/1389450033491055
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发表时间：
2003-05
影响因子：
3.2
通讯作者：
N. Tomita;H. Azuma;Y. Kaneda;T. Ogihara;R. Morishita
中科院分区：
文献类型：
--
作者：
N. Tomita;H. Azuma;Y. Kaneda;T. Ogihara;R. Morishita
在发达国家，包括肾脏疾病在内的心血管疾病是死亡和发病的主要原因。大多数传统疗法效率低下，往往治疗症状，而不是疾病的根本原因。基于寡核苷酸的基因治疗为心血管疾病的预防和治疗提供了新的途径。将基因导入体细胞以干扰导致心血管疾病的发病机制可能为更好地预防和治疗心血管疾病提供新的途径。基因转移技术的重大发展对心血管疾病（包括肾脏疾病）基因治疗潜力的深入研究做出了重要贡献。分子生物学的惊人进步为将靶基因转移到体细胞中所必需的技术提供了巨大的改进。基因转移方法已经得到了令人惊讶的改进。事实上，它们中的一些（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。分子生物学的最新进展为抑制靶基因表达提供了新的技术。特别是，应用DNA技术如反义策略来调节体内疾病相关基因的转录具有重要的治疗潜力。近年来，顺式反义双链寡核苷酸转染作为一种新的抗基因策略被广泛应用于基因治疗。对应于顺式序列的双链ODN的转染将导致真实的顺式-反式相互作用的减弱，导致从内源性顺式元件中去除反式因子，随后调节基因表达。
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.