Transcription factors as molecular targets: molecular mechanisms of decoy ODN and their design.
Transcription factors as molecular targets: molecular mechanisms of decoy ODN and their design.
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DOI：
10.2174/1389450033490803
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发表时间：
2003-10
影响因子：
3.2
通讯作者：
N. Tomita;T. Ogihara;R. Morishita
中科院分区：
文献类型：
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作者：
N. Tomita;T. Ogihara;R. Morishita
细胞和分子研究的最新进展为以DNA技术为基础的抑制靶基因表达提供了新的技术，如反义寡核苷酸(ODN)或诱骗ODN。特别是，应用反义策略在体内调控疾病相关基因的转录，对于治疗或治愈各种疾病和异常生理状况具有重要的治疗潜力。另一方面，最近，一种成功的基于ODN的方法被称为诱骗ODN，它使用含有能够穿透细胞的增强子元件的合成ODN与序列特异性DNA结合蛋白结合，并干扰体内外的转录。顺式元件双链诱骗ODN作为基因治疗或检测特定基因表达的分子机制的研究工具，已被报道成为一类新型抗基因策略中的新的强有力的工具。与顺式序列对应的双链ODN的转染将导致真正的顺式-反式相互作用的减弱，导致反式因子从内源性顺式元件中去除，从而调节基因的表达。到目前为止，我们已经选择了几个靶转录因子NFkappaB(核因子-kappaB)和E2F来阻止疾病的进展，并选择了肾素基因的负调控元件(NRE)和血管紧张素原基因激活元件(AGE)来研究基因表达的分子机制。在这一部分中，我们介绍了诱骗策略的原理以及如何设计诱骗ODN。
Recent progress in cellular and molecular research has provided a new technique to inhibit target gene expression based on DNA technology such as antisense oligonucleotides (ODN) or decoy ODN. Especially, application of an antisense strategy to regulate the transcription of disease-related genes in vivo has important therapeutic potential to treat or cure a variety of diseases and abnormal physiological conditions. On the other hand, recently, a successful ODN-based approach termed decoy ODN has used synthetic ODN containing an enhancer element that can penetrate cells, to bind to sequence-specific DNA-binding proteins and interfere with transcription in vitro and in vivo. Transfection of cis-element double-stranded decoy ODN has been reported as a new powerful tool in a new class of anti-gene strategies to treat various diseases as gene therapy or as a research tool to examine the molecular mechanisms of expression of a specific gene. 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. To date, we have chosen several target transcription factors such as NFkappaB (nuclear factor-kappaB) and E2F to prevent the progression of diseases, and negative regulatory element (NRE) for the renin gene and angiotensinogen gene-activating element (AGE) for the angiotensinogen gene to examine the molecular mechanisms of gene expression. In this section, we introduce the principles of the decoy strategy and how to design decoy ODN.