Table 1.
Alzheimer’s disease therapeutics using the CRISPR–Cas9 system.
| Targeted Genes | Experimental Model | Findings |
|---|---|---|
| Amyloid precursor protein (APP) |
Tg2576 mice [101] | APP and Aβ reduction |
| cell and animal models [102] | β-cleavage and Aβ production attenuation | |
| human induced pluripotent stem cells [103] | disease model | |
| cell line [104] | a model of γ-secretase substrate recognition and Notch receptors | |
| 3′-UTR APP | C57BL/6 mice [105] | APP and Aβ reduction |
| Presenilin 1 (PSEN1) |
human induced pluripotent stem cells [103] | disease models generated by CRISPR |
| SH-SY5Y neuroblastoma cells [106] | identification of homozygous and heterozygous mutations | |
| Presenilin 2 (PSEN2) |
human basal forebrain cholinergic neurons [107] | reduced Aβ42/40 ratio |
| human basal forebrain cholinergic neurons [108] | normalization of Aβ levels | |
| Beta-secretase 1 (BACE1) |
5 × FAD Alzheimer’s mouse model [109] | reduction of APP, Aβ and cognitive impairment |
| BACE1 and tyrosine hydroxylase (Th) |
cell line [110] | Reduction of BACE1, Aβ production and Th |
| Apolipoprotein E (APOE) |
induced pluripotent stem cells [111] | reduction of Aβ deposition and hyper-phosphorylation of tau protein, increased turning of APOE4 to APOE3 |
| human and murine cell lines [112] | permanent correction of ~15–75% of total cellular DNA with minimal indel formation | |
| γ-secretase activating protein (GSAP) |
HEK-APP cell line [113] | reduces γ-secretase activity for Aβ production, but not for Notch1 cleavage |
APP, amyloid precursor protein; Aβ, amyloid β; PSEN1, presenilin 1; PSEN2, presenilin 2; CRISPR–Cas9 system, clustered regulatory interspaced short palindromic repeats-associated protein 9; BACE1, beta-secretase 1; APOE, apolipoprotein E; DNA, deoxyribonucleic acid; GSAP, γ-secretase activating protein; Th, tyrosine hydroxylase.