 For example, the well-studied Krüppel associated box (KRAB) domain can be fused to dCas9 to repress transcription of the target gene up to 99% in human cells.Whereas genome-editing by the catalytically active Cas9 nuclease can be accompanied by irreversible off-target genomic alterations, CRISPRi is highly specific with minimal off-target reversible effects for two distinct sgRNA sequences.Nonetheless, several methods have been developed to improve the efficiency of transcriptional modulation.