ANTISENSE GENE INHIBITION BY OLIGONUCLEOTIDES CONTAINING C-5 PROPYNE PYRIMIDINES
ANTISENSE GENE INHIBITION BY OLIGONUCLEOTIDES CONTAINING C-5 PROPYNE PYRIMIDINES
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DOI：
10.1126/science.7684856
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发表时间：
1993-06-04
期刊：
影响因子：
56.9
通讯作者：
FROEHLER, BC
中科院分区：
文献类型：
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作者：
WAGNER, RW;MATTEUCCI, MD;FROEHLER, BC
含有尿苷和胞苷的C-5丙炔类似物的硫代磷酸寡脱氧核苷酸以高亲和力结合RNA，是基因表达的有效反义抑制剂。在细胞分析中，基因特异性反义抑制发生在纳摩尔浓度的寡核苷酸，是剂量依赖性的和精致的序列错配敏感，并与解链温度和寡核苷酸的长度。活性是独立的RNA靶位点和细胞类型，但只有当寡核苷酸显微注射或交付细胞透化剂是可检测的。这些寡核苷酸可能在治疗和基因功能研究中具有重要的应用。
Phosphorothioate oligodeoxynucleotides containing the C-5 propyne analogs of uridine and cytidine bind RNA with high affinity and are potent antisense inhibitors of gene expression. In a cellular assay, gene-specific antisense inhibition occurred at nanomolar concentrations of oligonucleotide, was dose-dependent and exquisitely sensitive to sequence mismatches, and was correlated with the melting temperature and length of oligonucleotide. Activity was independent of RNA target site and cell type but was detectable only when the oligonucleotides were microinjected or delivered with cell-permeabilizing agents. These oligonucleotides may have important applications in therapy and in studies of gene function.