Table 1.

Comparison of screening platforms

Characteristic	CRISPRn	CRISPRi	RNAi (miRNA-based shRNAs)	CRISPRa
Effect	Knockout (KO)	Knockdown (KD)	Knockdown (KD)	Activation
Mechanism	Indel, mutation	Transcriptional interference	Transcript degradation, translational interference	Transcriptional activation
Guide target choice	Anywhere in the genome (PAM)	Transcription start site (TSS; PAM)	Exons	Transcription start site (TSS; PAM)
Target selectivity	Can distinguish any target	Depends on TSS, cannot distinguish products derived from the same transcript	Can distinguish splice variants	Depends on TSS, cannot distinguish products derived from the same transcript
Highly amplified regions (genes)	Off-target effects: DSBs evoke DNA damage repair, resulting in cell cycle arrest independent of target	Can be targeted if all use the same TSS	Can be targeted	Can be targeted if all use the same TSS
Distinguish alternative TSSs	Possible	Yes	Possible	Yes
Distinguish transcript splice variants	Possible	No	Possible	No
Performance of individual sgRNAs or shRNAs	Most work	Many work	Requires good prediction tools or testing	Many work