Use of antisense oligonucleotides in functional genomics and target validation.

Use of antisense oligonucleotides in functional genomics and target validation.
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反义寡核苷酸在功能基因组学和靶标验证中的应用。

DOI:
10.1089/154545704322988058
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发表时间:
2004
期刊:
影响因子:
--
通讯作者:
E. Marcusson
E. Marcusson
中科院分区:
--
文献类型:
--
作者:
L. V. Ravichandran;N. Dean;E. Marcusson

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随着人类基因组测序的完成,大量的兴趣已经转移到基于功能基因组学的研究,以鉴定用于治疗各种疾病的新型药物靶标。制药业面临的主要挑战是确定致病基因和阐明已知功能基因的其他作用。基因功能化和靶点验证可能是识别新的潜在药物靶点的最重要步骤。本文综述了反义技术的最新进展及其在快速识别和验证新药靶点中的应用。该技术作为药物发现过程的开始的重要性和适用性通过相关的基于细胞培养的测定和特定动物疾病模型中的正相关性来强调。一些用于验证基因靶点的反义抑制剂本身正在被开发为药物。目前的临床试验的基础上,在很短的时间内确定的这些线索,进一步证实了反义技术为基础的功能基因组学的重要性,作为一个组成部分的目标验证和药物靶点识别。
With the completion of sequencing of the human genome, a great deal of interest has been shifted toward functional genomics-based research for identification of novel drug targets for treatment of various diseases. The major challenge facing the pharmaceutical industry is to identify disease-causing genes and elucidate additional roles for genes of known functions. Gene functionalization and target validation are probably the most important steps involved in identifying novel potential drug targets. This review focuses on recent advances in antisense technology and its use for rapid identification and validation of new drug targets. The significance and applicability of this technology as a beginning of the drug discovery process are underscored by relevant cell culture-based assays and positive correlation in specific animal disease models. Some of the antisense inhibitors used to validate gene targets are themselves being developed as drugs. The current clinical trials based on such leads that were identified in a very short time further substantiate the importance of antisense technology-based functional genomics as an integral part of target validation and drug target identification.
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