miCas9 is a fusion protein of the wild type Streptococcus pyogenes Cas9 (spCas9) with a 36 amino acid long fragment coded by BRCA2 exon 27 (Brex27). In comparison to spCas9, mi-spCas9 satisfactorily improved the efficacy and safety performances: (i) it increases large size gene knock-in rate by multiple folds; (ii) it reduces off-target indel rate; and importantly, it reduces undesirable on-target indel rate, the first nuclease that effectively achieves this to the best of our knowledge. The fusion motif, Brex27, can be used as a plug-&-play module to improve other GENs. (Ma et al., Nat Commun 2020, 11:6082)