Table 2.

Summary of gene editing approaches to treat dyslipidemias.

Target	Model	Method	Results	Reference

LDLR	Mouse, C57BL/6J	AAV-CRISPR/SaCas9 disruption	Severe hypercholesterolemia Atherosclerotic lesions in aortas	Jarrett, K. E. 2018 (21)
	Mouse, C57BL/6	CRISPR/SpCas9 HDR into fertilized eggs	Elevated plasma cholesterol Atherosclerotic lesions in aortas	Zhao, H. 2020 (23)
	Mouse, Ldlr^E208X Knock-in	Dual AAVs-CRISPR/SpCas9 HDR	18% restoration LDLR protein ~65% decrease cholesterol Smaller atherosclerotic lesions in aortas	Zhao, H. 2020 (23)
	Human iPSC, FH Patient	CRISPR/SpCas9 Nickase, HDR repair	Restored normal LDLR structure	Omer, L. 2017 (63)

LDLR + APOB	Mouse, Cas9 Transgenic	AAV disruption	Reduced plasma cholesterol Protection against atherosclerosis	Jarrett, K. E. 2017 (64)

PCSK9	Mouse, C57BL/6	Adenovirus-CRISPR/SpCas9 disruption	90% decrease PCSK9 protein 35–40% decrease plasma cholesterol	Ding, Q. 2014 (84)
	Mouse, C57BL/6	AAV-CRISPR/SaCas9 disruption	~95% decrease PCSK9 protein ~40% decrease plasma cholesterol	Ran, F. 2015 (53)
	Mouse, C57BL/6	LNP-CRISPR/SpCas9 disruption	Undetectable PCSK9 protein 35–40% decrease plasma cholestero	Yin, H. 2017 (87)
	Mouse, C57BL/6J	Adenovirus-BE3 base editing disruption	~55% decrease PCSK9 protein ~30% decrease plasma cholesterol	Chadwick, A. C. 2017 (88)
	Mouse, C57BL/6	Dual AAVs-CBE base editing disruption	~20–25% editing efficiency Pcsk9 38% editing in liver overall	Levy, J. M. 2020 (89)
	Mouse, Chimeric Liver-Humanized	Adenovirus-CRISPR/SpCas9 disruption	52% decrease human PCSK9 protein	Wang, X. 2016 (86)
	Non-human primate, Rhesus macaque	AAV-1^st generation meganuclease disruption	Up to 84% decrease PCSK9 protein Up to 60% decrease LDL-C	Wang, L. 2018 (24)
	Non-human primate, Rhesus macaque	AAV-2^nd generation meganuclease disruption	55–62% decrease PCSK9 protein 33–39% decrease LDL-C	Wang, L. 2018 (24)
	Non-human primate, Rhesus macaque	AAV-2^nd generation meganuclease (self-targeting) disruption	24–60% decrease PCSK9 protein 11–36% decrease LDL-C	Breton, C. 2021 (90)
	Non-human primate, Cynomolgus macaque	LNP-ABE base editing disruption	32% decrease PCSK9 protein 14% decrease LDL-C	Rothgangl, T. 2021 (46)
	Non-human primate, Cynomolgus macaque	LNP-ABE8.8 base editing disruption	81–90% decrease PCSK9 proteinn 60–65% decrease LDL-C	Musunuru, K. 2021 (47)

ANGPTL3	Mouse, C57BL/6	LNP-CRISPR/SpCas9 disruption	65% decrease ANTPL3 protein 56% decrease LDL-C 29% decrease TG	Qiu, M. 2021 (96)
	Mouse, C57BL/6J	Adenovirus-BE3 base editing disruption	49% decrease ANGPTL3 protein 19% decrease cholesterol 31% decrease TG	Chadwick, A. C. 2018 (97)
	Mouse, Ldlr Knockout	Adenovirus-BE3 base editing disruption	51% decrease cholesterol 56% decrease TG	Chadwick, A. C. 2018 (97)
	Non-human primate	LNP-ABE base editing disruption	95% decrease ANGPTL3 protein 19% decrease LDL-C 64% decrease TG	Verve Therapeutics (98)

PCSK9 + ANGPTL3	Mouse, C57BL/6J	Adenovirus-BE3 base editing disruption	~20% decrease cholesterol ~20–30% decrease TG	Chadwick, A. C. 2018 (97)

APOC3	Hamster, Syrian Golden	CRISPR/Cas9 disruption	~50% decrease TG Some protection against atherosclerosis	Guo, M. 2020 (102)
APOC3	Rabbit, New Zealand White	CRISPR/Cas9 disruption	50% decrease TG Protection against atherosclerosis	Zha, Y, 2021 (103)

AAV, adeno-associated virus; ANGPTL3, angiopoietin-like 3; APOB, apolipoprotein B; APOC3, apolipoprotein C3; CRISPR/CAS, clustered regularly interspaced short palindromic repeats /CRISPR-associated; HDR, homology-directed repair; LDL-C, low density lipoprotein cholesterol; LDLR, low density lipoprotein receptor; LNP, lipid nanoparticle; PCSK9, proprotein convertase subtilisin/kexin type 9; SaCas9, Staphylococcus aureus Cas9; SpCas9, Streptococcus pyogenes Cas9; TG, triglyceride.