Abstract
In recent years, the vital role of genetic factors in human diseases have been widely recognized by scholars with the deepening of life science research, accompanied by the rapid development of gene-editing technology. In early years, scientists used homologous recombination technology to establish gene knock-out and gene knock-in animal models, and then appeared the second-generation gene-editing technology zinc-finger nucleases (ZFNs) and transcription activator–like effector nucleases (TALENs) that relied on nucleic acid binding proteins and endonucleases and the third-generation gene-editing technology that functioned through protein–nucleic acids complexes—CRISPR/Cas9 system. This holds another promise for refractory diseases and genetic diseases. Cardiovascular disease (CVD) has always been the focus of clinical and basic research because of its high incidence and high disability rate, which seriously affects the long-term survival and quality of life of patients. Because some inherited cardiovascular diseases do not respond well to drug and surgical treatment, researchers are trying to use rapidly developing genetic techniques to develop initial attempts. However, significant obstacles to clinical application of gene therapy still exists, such as insufficient understanding of the nature of cardiovascular disease, limitations of genetic technology, or ethical concerns. This review mainly introduces the types and mechanisms of gene-editing techniques, ethical concerns of gene therapy, the application of gene therapy in atherosclerosis and inheritable cardiovascular diseases, in-stent restenosis, and delivering systems.
Highlights
Genome editing technologies are continually emerging and evolving in recent years, leading to fundamental upgrades of the biomedical research model
This study shows great potential for geneediting in liver cells to treat Familial Hypercholesterolemia (FH), but the unsatisfactory editing efficiency and undesired off-target effect should be addressed before clinical application
3 of 5 patients decreased total cholesterol (6–20%) 3 of 5 patients decreased LDL (6–25%) 3 of 5 patients decreased ApoB (10–21%) Restored Ldlr mRNA level (11% of wild-type) Restored low-density lipoprotein receptor (LDLR) protein level (18% of wild-type) Decreased atherosclerotic lesion area Alleviated lipid accumulation Decreased macrophage infiltration Decreased plaque fibrosis Reduction in pulmonary vascular resistance (TPVR:38% and pulmonary vascular resistance index (PVRI): 48%), Reduction in vascular smooth muscle area per unit area of visual field (40%) Reduction in abnormally elevated TGF-β signaling by ∼29%
Summary
Genome editing technologies are continually emerging and evolving in recent years, leading to fundamental upgrades of the biomedical research model. Compared with the 2nd-generation (ZFNs and TALENs) gene-editing technology, the 3rd-generation CRISPR/Cas9 relies on RNA-DNA interaction rather than protein-DNA interaction for target site recognition, dramatically improving geneediting accuracy.
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