小分子触发的 Cas9 蛋白，提高了基因组编辑的特异性。

1] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA.

Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Nat Chem Biol. 2015 May;11(5):316-8. doi: 10.1038/nchembio.1793. Epub 2015 Apr 6.

Directly modulating the activity of genome-editing proteins has the potential to increase their specificity by reducing activity following target locus modification. We developed Cas9 nucleases that are activated by the presence of a cell-permeable small molecule by inserting an evolved 4-hydroxytamoxifen-responsive intein at specific positions in Cas9. In human cells, conditionally active Cas9s modify target genomic sites with up to 25-fold higher specificity than wild-type Cas9.

直接调节基因组编辑蛋白的活性有可能通过减少靶标基因修饰后活性来提高其特异性。我们通过在 Cas9 的特定位置插入经过进化的 4-羟基他莫昔芬反应性内含肽，开发出了可被细胞通透的小分子激活的 Cas9 核酸酶。在人细胞中，条件性激活的 Cas9 修饰靶基因座的特异性比野生型 Cas9 高 25 倍。