Disclosed and claimed are mutation(s) or modification(s) of the CRISPR enzyme, for example a Cas enzyme such as a Cas9, which obtain an improvement, for instance a reduction, as to off-target effects of a CRISPR-Cas or CRISPR-enzyme or CRISPR-Cas9 system or complex containing or including such a mutated or modified Cas or CRISPR enzyme or Cas9. Methods for making and using and uses of such mutated or modified Cas or CRISPR enzyme or Cas9 and systems or complexes containing the same and products from such methods and uses are also disclosed and claimed.在此揭露並且要求保護CRISPR酶、例如Cas酶比如Cas9的一個或多個突變或一種或多種修飾,該等突變或修飾就含有或包括這樣一種經突變或修飾的Cas或CRISPR酶或Cas9的CRISPR-Cas或CRISPR酶或者CRISPR-Cas9系統或複合物的脫靶效應而言獲得改進,例如降低脫靶效應。還揭露並且要求保護用於製備和使用這樣的含有該等突變或修飾的經突變或修飾的Cas或CRISPR酶或Cas9和系統或複合物的方法和這樣的含有該等突變或修飾的經突變或修飾的Cas或CRISPR酶或Cas9和系統或複合物的用途以及來自這樣的方法和用途的產物。