Different approaches for efficient gene activation using CRISPRa. (A) dCas9 fused to the VP64 viral repeat domain. (B) CRISPR SunTag, comprising multiple copies of VP64 fused to a protein scaffold and recruited to dCas9. (C) dCas9 fused to the VP196 viral repeat domain containing more repeats than VP64. (D) Synergistic activation mediator (SAM), comprising dCas9 fused to VP64 and a modified sgRNA fused to MS2, p65, and HSF1. (E) VPR, comprising dCas9 fused to VP64, p65, and Rta. (F) CRISPR-on, comprising dCas9 fused to TET1 to reverse the repressive methylation effect caused by CRISPR-off (See Section 2.2 and Figure 3G above). (G) dCas9 fused to p300 leading to H3K27 acetylation for gene transactivation. (H) enCRISPRa, comprising dCas9 fused to p300 and a modified sgRNA fused to MS2 and VP64. (Created with BioRender.com (accessed on 12 December 2021)).