Advances in CRISPR/Cas gene editing and its applications in cardiovascular diseases

doi:10.3969/j.issn.1674-8115.2026.03.010

Abstract

Abstract:

Gene editing technologies refer to a class of techniques capable of precisely modifying or manipulating the genome or transcriptome of living organisms. Over the past decade, next-generation gene editing tools, represented by CRISPR/Cas9, have rapidly advanced, demonstrating superior efficiency, safety, and broader applicability compared to traditional methods, such as zinc finger nuclease (ZFN) and transcription activator-like effector nuclease (TALEN). These advancements have facilitated the transition of gene editing from basic research to clinical applications. Cardiovascular diseases remain a leading cause of global mortality and health burden, yet current treatments face challenges such as undruggable targets, significant side effects, and limited efficacy. For certain conditions that are difficult to treat with conventional pharmacotherapy, gene editing offers a novel therapeutic approach. Currently, this technology has been successfully applied to drug development for diseases such as transthyretin amyloidosis and hyperlipidemia, with pioneering candidates such as NTLA-2001 and CTX310 having entered clinical trials. Mitigating immune responses and off-target effects, along with overcoming cardiac-targeted delivery barriers, are pivotal for clinical translation. With advancements in artificial intelligence-assisted design and non-viral vectors, CRISPR/Cas technology is expected to overcome current liver-predominant limitations, paving the way for in situ cardiac treatment and offering a curative strategy for cardiovascular diseases. This article systematically reviews the structure and mechanism of CRISPR/Cas systems and summarizes recent advances in their applications to cardiovascular diseases, including gene knockout, epigenetic editing, base editing, prime editing, and RNA editing, aiming to provide important references for subsequent research and clinical translation in this field.

Key words: gene editing, cardiovascular disease, CRISPR/Cas

CLC Number:

Tian Qijia, Jia Kangni, Yan Xiaoxiang. Advances in CRISPR/Cas gene editing and its applications in cardiovascular diseases[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(3): 358-367.

Figures/Tables 2

TrendMD

References 76

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Treatment	Gene editing method	Indication	Target gene	Delivery method	Clinical trial ID	Phase	Efficacy	Follow-up	Safety	Reference
NTLA-2001	CRISPR/Cas9 knock out	ATTR-CM	TTR	LNP	NCT06128629	Ⅲ	TTR reduction: 89% (Day 28), 90% (Month 12)	87% reduction sustained (Month 36)	Most common treatment-related AEs: mild infusion-related reactions (14%) and transient liver enzyme elevations (6%)	[6-7]
YOLT-201	CRISPR/Cas9 knock out	ATTR-CM	TTR	LNP	NCT06539208	Ⅰ/Ⅱa	Trial ongoing	\	\	[38]
ART001	CRISPR/Cas9 knock out	ATTR-CM	TTR	LNP	ChiCTR2400081216	Ⅰ	Trial ongoing	\	\	[39]
YOLT-101	Base editing	Familial hypercholesterolemia	PCSK9	GalNAc-LNP	NCT06458010	Ⅰ	High-dose (0.6 mg/kg): PCSK9 reduced by 72.5% and LDL-C by 50.4% (Month 4)	Follow-up ongoing	Most common treatment-related AEs; mild infusion-related reactions (83%) and transient liver enzyme elevations (50%)	[40]
VERVE-101	Base editing	Familial hypercholesterolemia	PCSK9	LNP	NCT05398029	Ⅰ	High-dose (0.6 mg/kg): PCSK9 reduced by 47% and LDL-C by 55% (Day 28); sustained through 180 d	Follow-up ongoing	Treatment-related Grade 3 serious AEs: transient liver enzyme elevations and thrombocytopenia; mild infusion-related reactions were common; trial enrollment paused due to safety concerns	[25]
VERVE-102	Base editing	Familial hypercholesterolemia or premature coronary artery disease	PCSK9	GalNAc-LNP	NCT06164730	Ⅰ	Trial ongoing	\	\	[41]
CTX320	CRISPR/Cas9 knock out	Atherosclerosis or calcific aortic valve stenosis	LPA	LNP	ACTRN12623001095651	Ⅰ	Trial ongoing	\	\	[42]
CTX310	CRISPR/Cas9 knock out	Refractory dyslipidemias	ANGPTL3	LNP	ACTRN12623000809639	Ⅰ	High-dose (0.8 mg/kg): ANGPTL3 reduced by 73.2%, LDL-C by 48.9%, and triglycerides by 55.2% (Day 60)	Follow-up ongoing	Most common treatment-related AEs: mild infusion-related reactions (20%) and transient liver enzyme elevations (7%)	[9]
VERVE-201	Base editing	Refractory hypercholesterolemia	ANGPTL3	GalNAc-LNP	NCT06451770	Ⅰ	Trial ongoing	\	\	[43]

Treatment	Gene editing method	Indication	Target gene	Delivery method	Clinical trial ID	Phase	Efficacy	Follow-up	Safety	Reference
NTLA-2001	CRISPR/Cas9 knock out	ATTR-CM	TTR	LNP	NCT06128629	Ⅲ	TTR reduction: 89% (Day 28), 90% (Month 12)	87% reduction sustained (Month 36)	Most common treatment-related AEs: mild infusion-related reactions (14%) and transient liver enzyme elevations (6%)	[6-7]
YOLT-201	CRISPR/Cas9 knock out	ATTR-CM	TTR	LNP	NCT06539208	Ⅰ/Ⅱa	Trial ongoing	\	\	[38]
ART001	CRISPR/Cas9 knock out	ATTR-CM	TTR	LNP	ChiCTR2400081216	Ⅰ	Trial ongoing	\	\	[39]
YOLT-101	Base editing	Familial hypercholesterolemia	PCSK9	GalNAc-LNP	NCT06458010	Ⅰ	High-dose (0.6 mg/kg): PCSK9 reduced by 72.5% and LDL-C by 50.4% (Month 4)	Follow-up ongoing	Most common treatment-related AEs; mild infusion-related reactions (83%) and transient liver enzyme elevations (50%)	[40]
VERVE-101	Base editing	Familial hypercholesterolemia	PCSK9	LNP	NCT05398029	Ⅰ	High-dose (0.6 mg/kg): PCSK9 reduced by 47% and LDL-C by 55% (Day 28); sustained through 180 d	Follow-up ongoing	Treatment-related Grade 3 serious AEs: transient liver enzyme elevations and thrombocytopenia; mild infusion-related reactions were common; trial enrollment paused due to safety concerns	[25]
VERVE-102	Base editing	Familial hypercholesterolemia or premature coronary artery disease	PCSK9	GalNAc-LNP	NCT06164730	Ⅰ	Trial ongoing	\	\	[41]
CTX320	CRISPR/Cas9 knock out	Atherosclerosis or calcific aortic valve stenosis	LPA	LNP	ACTRN12623001095651	Ⅰ	Trial ongoing	\	\	[42]
CTX310	CRISPR/Cas9 knock out	Refractory dyslipidemias	ANGPTL3	LNP	ACTRN12623000809639	Ⅰ	High-dose (0.8 mg/kg): ANGPTL3 reduced by 73.2%, LDL-C by 48.9%, and triglycerides by 55.2% (Day 60)	Follow-up ongoing	Most common treatment-related AEs: mild infusion-related reactions (20%) and transient liver enzyme elevations (7%)	[9]
VERVE-201	Base editing	Refractory hypercholesterolemia	ANGPTL3	GalNAc-LNP	NCT06451770	Ⅰ	Trial ongoing	\	\	[43]