单链 microRNA 模拟物。
Single-stranded microRNA mimics.
机构信息
Sirna Therapeutics, a wholly owned subsidiary of Merck & Co., San Francisco, California 94158, USA.
出版信息
RNA. 2012 Oct;18(10):1796-804. doi: 10.1261/rna.031278.111. Epub 2012 Aug 21.
Abstract
miRNAs are ∼22-nt RNAs that bind to the Argonaute family of proteins and have important regulatory roles in plants and animals. Here, we show that miRNAs exhibit targeting activity in cells when delivered as single strands that are 5'-phosphorylated and that contain 2'-fluoro ribose modifications. Length preferences, chemical modification sensitivity, and genome-wide seed-based targeting all suggest that this activity is Ago-based. Activity could be enhanced by annealing of segmented passenger strands containing non-nucleic acid spacers. Furthermore, screening of randomly generated sequences identified pyrimidine rich 3' cassette sequences that increased single strand activity. These results provide an initial step in the development of single-stranded miRNA mimics for therapeutic use.
摘要
miRNAs 是一种约 22 个核苷酸的 RNA，它可以与 Argonaute 家族蛋白结合，在动植物中具有重要的调控作用。在这里，我们展示了 miRNA 作为单链在细胞中具有靶向活性，并且这些单链是 5'-磷酸化的，并含有 2'-氟核糖修饰。长度偏好、化学修饰敏感性和基于基因组种子的全基因组靶向都表明这种活性是基于 Ago 的。通过退火含有非核酸间隔区的分段过客链可以增强这种活性。此外，随机生成序列的筛选确定了富含嘧啶的 3' 盒序列，这些序列增加了单链的活性。这些结果为开发用于治疗的单链 miRNA 模拟物提供了初步步骤。
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