To provide CRISPR enzymes which achieve an improvement, for instance a reduction, as to off-target effects of a CRISPR-Cas or CRISPR-enzyme or CRISPR-Cas9 system.SOLUTION: Provided herein are one or more mutations or one or more modifications of a Cas enzyme such as a Cas9, or a complex containing or including the mutated or modified Cas or CRISPR enzyme or Cas9. Also provided are methods for making and using and uses of the mutated or modified Cas or CRISPR enzyme or Cas9 and systems or complexes containing the same, and products from such methods and uses.SELECTED DRAWING: None【課題】CRISPR-Cas又はCRISPR酵素又はCRISPR-Cas9系のオフターゲット効果に関して改善、例えば低下を達成する、CRISPR酵素の提供。【解決手段】Cas9などのCas酵素の1つ又は複数の突然変異又は1つ又は複数の改変、又は突然変異した又は改変されたCas又はCRISPR酵素又はCas9を含有する又はそれを含む複合体の提供。さらに突然変異した又は改変されたCas又はCRISPR酵素又はCas9及びそれを含有する系又は複合体の作製及び使用方法並びに使用、及びかかる方法及び使用からの産物の提供。【選択図】なし