Table 1.

Comparative overview of gene editing interventions on LDLR.

Author	Study design	Method	Findings	Treatment-related adverse effects
Carlson et al. [36]	Pig	TALEN	Biallelic inactivation of LDLR in 10 out of 11 animals	-
Huang et al. [37]	Pig	CRISPR/Cas9	Biallelic inactivation of ApoE and LDLR in all animals	No off-target mutations were found.
			Elevated plasma levels of LDL-C, ApoB, and TC
Omer et al. [38]	Human iPSC	CRISPR/Cas9	Both alleles of 83% of enriched clones were corrected	No off-target mutations were detected.
Jarrett et al. [39]	Cas9 transgenic mice	AAV-CRISPR	LDLR disruption led to hypercholesteremia and atherosclerosis	Off-target sites were found for the LDLR gene, but not ApoB.
			ApoB disruption led to lower levels of cholesterol	Mice received LDLR + ApoB gRNAs showed evidence of microvesicular steatosis.
Zhao et al. [40]	LdlrE⁢208⁢X mouse	AAV-CRISPR/Cas9	LDLR expression restored partly	Most of off-target mutations were found in introns of different genes.
			Lowered plasma levels of cholesterol, TG, and LDL-C

LDLR, low density lipoprotein receptor; CRISPR, clustered regularly interspaced short palindromic repeats; Cas9, CRISPR-associated protein 9; TALEN, transcription activator-like effector nuclease; ApoB, apolipoprotein B; ApoE, apolipoprotein E; LDL-C, low density lipoprotein cholesterol; TG, triglyceride; iPSC, induced-pluripotent stem cell; AAV, adeno-associated virus; gRNAs, guide RNAs; TC, total cholesterol.