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Methods and compositions for silencing gene families using artificial microRNAs

机译:使用人工microRNA沉默基因家族的方法和组合物

摘要

Methods and compositions are provided which allow for a single microRNA (miRNA) to reduce the level of expression of at least two members of the same protein and/or gene family. While a single 21 base pair miRNA can cause cleavage of a variety of species of mRNAs, an entire gene family cannot be silenced unless that gene family shares near identity within a 21 base pair region that is also able to be cleaved by a single miRNA. In certain embodiments, all members of a given protein and/or gene family can be suppressed with a miRNA expression construct disclosed herein even if they do not share near identity within a 21 base pair region that is also able to function as a miRNA. Such methods and compositions employ miRNA expression constructs having a structure such that the most abundant form of miRNA produced from the construct is a 22-nucleotide miRNA. The 22-nucleotide miRNA produced from the miRNA expression construct thereby reduces the level of expression of not only the target sequence for the miRNA, but also reduces the level of expression of at least one additional sequence from the same protein and/or gene family as the target sequence.
机译:提供了允许单个微RNA(miRNA)降低相同蛋白质和/或基因家族的至少两个成员的表达水平的方法和组合物。虽然单个21个碱基对的miRNA可以引起多种mRNA的切割,但除非该基因家族在一个21个碱基对的区域内也具有相同的身份,该基因家族也可以被单个miRNA切割,否则该基因家族不能被沉默。在某些实施方案中,给定蛋白质和/或基因家族的所有成员可以用本文公开的miRNA表达构建体抑制,即使它们在也能够充当miRNA的21个碱基对区域内不共享近乎同一性。这样的方法和组合物使用具有这样的结构的miRNA表达构建体,使得从该构建体产生的最丰富形式的miRNA是22个核苷酸的miRNA。因此,由miRNA表达构建体产生的22个核苷酸的miRNA不仅降低了miRNA靶序列的表达水平,而且还降低了来自相同蛋白质和/或基因家族的至少一个其他序列的表达水平。目标序列。

著录项

  • 公开/公告号US9719102B2

    专利类型

  • 公开/公告日2017-08-01

    原文格式PDF

  • 申请/专利权人 E I DU PONT DE NEMOURS AND COMPANY;

    申请/专利号US201514716955

  • 发明设计人 BRIAN MCGONIGLE;

    申请日2015-05-20

  • 分类号C12N15/82;

  • 国家 US

  • 入库时间 2022-08-21 13:44:10

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