Table 1.

CRISPR/Cas systems used for lncRNA studies

Editing System	Advantages	Disadvantages	Cas Variant	Approach	Example lncRNAs	Reference
CRISPR/Cas9	Targeted deletion/mutation of gene to decrease lncRNA expression	Risk impacting the expression of adjacent or related genes	Cas9	Deletion of whole lncRNA loci	PINCR, Gm26878	(Chaudhary et al., 2017), (Szafranski et al., 2017)
			Cas9	Deletion of transcription factor binding sites	PURPL	(Li et al., 2017)
			Cas9	Deletion of large fragment of lncRNA locus	Rian	(Han et al., 2014)
			Cas9	Genome-wide screen via genomic deletion of lncRNA loci	-	(Zhu et al., 2016)
			Cas9	Genome-wide screen via deletion of lncRNA splice sites	-	(Liu et al., 2018)
CRISPRa	Overexpress lncRNA genes without permanent alteration of genome	Risk impacting the expression of adjacent genes	dCas9-VP64	Overexpression	MALAT1, NEAT1	(Xie et al., 2017), (Yamazaki et al., 2018), (Butler et al., 2019)
			dCas9-VP64	Genome-wide screen via CRISPR activation	-	(Bester et al., 2018)
CRISPRi	Repress lncRNA expression without permanent alteration of genome	Risk impacting the expression of adjacent genes	dCas9-KRAB	Knockdown	DIRC3, roX1, roX2	(Coe et al., 2019), (Ghosh et al., 2016)
			dCas9-KRAB, KRAB-dCas9	Genome-wide screen via knockdown of lncRNAs	-	(Liu et al., 2017), (Cai et al., 2020)
CRISPR/Cas13	Directly target lncRNA molecule	Transcription of lncRNA still occurs	Cas13d	Knockdown	HOTTIP, MALAT1	(Konnerman et al., 2018)
		Can only target ssRNA	dCas13b	Imaging	NEAT1, SatIII	(Yang et al., 2019)
			Cas13a	Genome-wide knockdown of lncRNAs	-	(Xu et al., 2020)