Table 2.
Experiments of gene therapy for atherosclerosis.
| References | Gene editing tool (Vector) | Disease (Target) | Animal model | Efficiency | Security |
|---|---|---|---|---|---|
| Ding et al. (92) | Crispr/Cas9 (ADV) | AS (PCSK9) | C57BL/6 mice | Mutagenesis rate of PCSK9: (>50%) Increased hepatic LDLR levels, Decreased plasma cholesterol levels |
No off-target mutagenesis was detected |
| Wang et al. (69) | Crispr/SpCas9 (ADV) | AS (PCSK9) | FRG KO Mouse with human hepatocytes | Mutagenesis rate of PCSK9: 42–47% Total cholesterol levels not changed. |
No off-target mutagenesis was detected |
| Musunuru et al. (93) | CRISPR Adenine base editor (lipid nanoparticles) |
AS (PCSK9) | Macaca fascicularis | Mean base editing frequency: 63% Decreased LDL level: 90% Decreased plasma cholesterol level: 60% |
One off-target editing site was detected (<1%) at the dose of 1.0 mg kg/L |
| Ran et al. (94) | Crispr/SaCas9 (AAV) | AS (PCSK9) | ApoB knockdown mouse | Mutagenesis rate of PCSK9: (>40%) Decreased total cholesterol levels: 40% |
No off-target mutagenesis was detected |
| Guo et al. (97) | CRISPR/Cas9 (vector is unknown) | AS (ApoC3) | Hamsters | Decreased triglyceride and total cholesterol; Decreased atherosclerotic lesion; Conversion of VLDL/LDL to HDL; |
Not report |
| Wacker et al. (102) | No gene editing (HDAd) | AS (ApoA1) | Rabbits | Decreased total cholesterol levels: 70% Decreased atherosclerotic lesion area Decreased Macrophage: 30% |
Not report |
| Hu et al. (105) | No gene editing (ADV) | AS (PPARγ) | ApoE−/− mice | Increased HDL level: 15.8% Decreased blood glucose level: 16.8% Decreased atherosclerotic lesion area Stabilized atherosclerotic plaque |
Not report |
| Inoue et al. (107) | No gene editing (Plasmid) | AS (MCP-1) | ApoE−/− mice | Decreased atherosclerotic lesion area Stabilized atherosclerotic plaque Decreased Immune cell infiltration |
Not report |
| Li et al. (109) | No gene editing (Lentivectors) | AS (LXRα) | LDLR−/− mice | Enhancing LXRα leads to: Decreased triglyceride: 50%; Decreased pro-inflammatory cytokines. Decreased atherosclerotic lesion area: 30%; |
Not report |
| Tontonoz et al. (113) | No gene editing (AAV8) | AS (LeXis) | LDLR−/− mice | Enhancing Lexis leads to: Decreased triglyceride and cholesterol Decreased atherosclerotic lesion area Protection of fatty liver |
No sign of hepatotoxicity was observed |
HDAd, helper-dependent adenoviral vector; AS, atherosclerosis; AAV, adeno-associated virus; ADV, adenovirus; LDL, low-density lipoprotein; LDLR, low-density lipoprotein receptor; HDL, high-density lipoprotein.