Table 3.
Experiments of gene therapy for hereditary cardiovascular diseases.
| Disease (Pathogenic gene) | References | Gene therapy method | Model | Efficiency | Security |
|---|---|---|---|---|---|
| MFS (FBN1) | Zeng et al. (2) | Crispr-BE | homozygous FBN1T7498C HEK293T Cells | 40% of mutants were corrected | 10% unpredicted base conversion occurred |
| Heterozygous FBN1T7498 embryos | 89% of mutants were corrected | 1 of 7 embryo showed unpredicted base conversion | |||
| FH (LDLR, APOB, PCSK9) | Grossman et al. (135) | Hepatocytes transfected by retroviruses; Transfected Hepatocytes were infused to portal vein |
Five patients with homozygous FH | 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%) |
Two of five patients developed perioperative myocardial ischemia No immune response occurred against to LDLR and retrovirus |
| Zhao et al. (63) | AAV8-CRISPR/Cas9 | LdlrE208X mice | Restored Ldlr mRNA level (11% of wild-type) Restored LDLR protein level (18% of wild-type) Decreased atherosclerotic lesion area Alleviated lipid accumulation Decreased macrophage infiltration Decreased plaque fibrosis |
Off-target sites were observed but located in introns of several genes No sign of liver injury detected. |
|
| HPAH (BMPR2) | Reynolds et al. (145) | ADV transgene | Chronic hypoxia rat model; Monocrotaline (MCT) rat model; |
Reduction in pulmonary vascular resistance (TPVR:38% and PVRI: 48%), Reduction in vascular smooth muscle area per unit area of visual field (40%) Reduction in abnormally elevated TGF-β signaling by ~29% |
MFS, marfan syndrome; FH, familial hypercholesterolemia; HPAH, heritable pulmonary artery hypertension.