| 摘要 |
<p>The invention relates to methods for targeting mutagenesis to a particular genomic region as well as related compositions and kits thereof. In an embodiment, the invention relates to a method for in vivo targeted mutagenesis comprising selectively introducing localised DNA damage into a genome in vivo, targeting a pathway requiring long-range resection so as to form a single-stranded region during biasing repair and selectively mutating the single stranded region. In another embodiment, the invention relates to a method of contacting a cell having an integrated array of DNA binding sites with a fusion protein of an array specific DNA binding domain and a DNA mutator enzyme domain. In another embodiment, the invention relates to a method of contacting a cell with a fusion protein of a DNA binding domain and a DNA nuclease domain, and further biasing repair of localised DNA damage by targeting a pathway requiring long-range resection. In another embodiment, the invention relates to a method of in vivo targeted mutagenesis, comprising delivering a Cas9 nuclease and a synthetic gRNA, and contacting the cell with a mutator.</p> |
