反义寡核苷酸在细胞培养、体内以及作为治疗剂方面的设计与应用。
Design and application of antisense oligonucleotides in cell culture, in vivo, and as therapeutic agents.
作者信息
Brysch W, Schlingensiepen K H
机构信息
Biognostik Ltd., Göttingen, Germany.
出版信息
Cell Mol Neurobiol. 1994 Oct;14(5):557-68. doi: 10.1007/BF02088837.
Abstract
- Synthetic oligonucleotides can inhibit the expression of a gene in a sequence specific manner on the transcriptional and translational level. These molecules are usually referred to as antisense oligonucleotides. 2. Antisense mediated inhibition of gene expression is a valuable tool to analyze the function of a gene in vivo and can also be used for therapeutic gene suppression. 3. A number of factors such as the mode of action, specificity, chemistry, and pharmacology must be carefully considered for the design and successful application of antisense oligonucleotides. 4. Assay systems and controls must be chosen as to assure that the observed biological effects of antisense oligonucleotides do in fact reflect the result of a specific gene inhibition. 5. This article critically discusses these factors in view of the literature and our own experience with a wide range of cell types and animal models, targeting different genes. The emphasis is on the use of phosphorothioate oligodeoxynucleotides in cell cultures, in vivo, and as potential drugs.
摘要
- 合成寡核苷酸可以在转录和翻译水平上以序列特异性方式抑制基因表达。这些分子通常被称为反义寡核苷酸。2. 反义介导的基因表达抑制是分析体内基因功能的一种有价值的工具，也可用于治疗性基因抑制。3. 在设计和成功应用反义寡核苷酸时，必须仔细考虑许多因素，如作用方式、特异性、化学性质和药理学。4. 必须选择测定系统和对照，以确保观察到的反义寡核苷酸的生物学效应确实反映了特定基因抑制的结果。5. 本文结合文献以及我们在针对不同基因的多种细胞类型和动物模型方面的经验，对这些因素进行了批判性讨论。重点是硫代磷酸酯寡脱氧核苷酸在细胞培养、体内以及作为潜在药物方面的应用。
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