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反义寡核苷酸对可变剪接的调控作为一种潜在的化疗方法:对基因表达的影响

Control of alternative splicing by antisense oligonucleotides as a potential chemotherapy: effects on gene expression.

作者信息

Mercatante Danielle R, Kole Ryszard

机构信息

Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

出版信息

Biochim Biophys Acta. 2002 Jul 18;1587(2-3):126-32. doi: 10.1016/s0925-4439(02)00075-3.

Abstract

Expression of alternatively spliced mRNA variants at specific stages of development or in specific cells and tissues contributes to the functional diversity of the human genome. Aberrations in alternative splicing were found as a cause or a contributing factor to the development, progression, or maintenance of various diseases including cancer. The use of antisense oligonucleotides to modify aberrant expression patterns of alternatively spliced mRNAs is a novel means of potentially controlling such diseases. However, to utilize antisense oligonucleotides as molecular chemotherapeutic agents, the global effects of these molecules need to be examined. The advent of gene expression array technology has now made it possible to simultaneously examine changes that occur in the expression levels of several thousand genes in response to antisense treatment. This analysis should help in the development of more specific and efficacious antisense oligonucleotides as molecular therapeutics.

摘要

可变剪接的mRNA变体在特定发育阶段或特定细胞及组织中的表达,有助于人类基因组的功能多样性。可变剪接异常被发现是包括癌症在内的各种疾病发生、发展或维持的原因或促成因素。使用反义寡核苷酸来改变可变剪接mRNA的异常表达模式,是一种潜在控制此类疾病的新方法。然而,要将反义寡核苷酸用作分子化疗药物,需要研究这些分子的整体效应。基因表达阵列技术的出现,使得同时检测数千个基因的表达水平因反义治疗而发生的变化成为可能。这种分析应有助于开发更特异、更有效的反义寡核苷酸作为分子治疗药物。

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