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Improved Methods of Genome Editing with and without Programmable Nucleases

机译:带有和不带有可编程核酸酶的基因组编辑的改进方法

摘要

The present invention includes compositions and methods for genome editing with in isolated cells or within an organism. The editing oligonucleotides contain an oligonucleotide strand which may contain a linker that positions an editing moiety in the proper location for modifying the targeted nucleobase and crisprRNA domain and an inactivated Cas 9 domain that cause deamination of the targeted nucleobase. The editing oligonucleotides may also contain at least one nucleotide sequence change from the targeted sequence in the genome. Certain embodiments of the method include modifying a genomic sequence within a cell utilizing an editing oligonucleotide without exogenous proteins to assist in the editing process. The editing oligonucleotide may comprise backbone modifications that increase the nuclease stability of the oligonucleotide as compared to unmodified oligonucleotides.
机译:本发明包括用于在分离的细胞内或生物体内进行基因组编辑的组合物和方法。编辑寡核苷酸包含寡核苷酸链,该寡核苷酸链可以包含接头,该接头将编辑部分定位在适当的位置上,以修饰目标核碱基和crispRNA结构域以及使目标核碱基脱氨基的失活的Cas 9结构域。编辑寡核苷酸还可以含有与基因组中的靶序列相比至少一个核苷酸序列变化。该方法的某些实施方案包括在没有外源蛋白质的情况下利用编辑寡核苷酸修饰细胞内的基因组序列,以辅助编辑过程。与未修饰的寡核苷酸相比,编辑寡核苷酸可包含主链修饰,其增加了寡核苷酸的核酸酶稳定性。

著录项

  • 公开/公告号US2019300872A1

    专利类型

  • 公开/公告日2019-10-03

    原文格式PDF

  • 申请/专利权人 TOD M. WOOLF;

    申请/专利号US201716099106

  • 发明设计人 TOD M. WOOLF;

    申请日2017-05-05

  • 分类号C12N15/10;A61K31/7115;A61K31/712;C12N15/11;

  • 国家 US

  • 入库时间 2022-08-21 12:09:07

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