Table 3 Precise genome-editing-mediated gene therapy
From: Precise genome-editing in human diseases: mechanisms, strategies and applications
Environment | Disease type | Target | Strategies | Editing efficiency | Delivery | References |
|---|---|---|---|---|---|---|
Ex vivo | Sickle cell disease | HBB | ZFN-HDR | ~18% T > A correction | Lentivirus and electroporation | |
Cas9-HDR | 20–30% T > A correction | AAV and electroporation | ||||
ABE | 40%–80% A > G correction | Electroporation | ||||
PE | ~27% T > A correction | Electroporation | ||||
β-thalassemia | IVS1 | ABE | ~80% A > G correction | Electroporation | ||
BCL11A, HBB | CBE | ~90% C > T correction of BCL11A, ~18.2 C > T correction of HBB | Electroporation | |||
BCL11A, HBG | ABE | ~94.3% A > G correction of BCL11A, ~85.5% A > G correction of HBG | Electroporation | |||
X-linked chronic granulomatous disease | CYBB | ZFN-HDR | ~7.1% CYBB cDNA insertion | AAV and electroporation | ||
Cas9-HDR | ~21% T > C correction | Electroporation | ||||
Lymphoblastic leukaemia | TRAC | Cas9-HDR | ~46.5% CAR insertion of T cells | AAV6 and electroporation | ||
Glioblastoma | AAVS1 | Cas9-HDR | >90% CAR insertion of cells | Nucleofection | ||
In vivo | Duchenne muscular dystrophy | DMD | HITI | 4% ~ 7% Exon 52 insertion | AAV9 | |
ABE | ~51.0% A > G correction | AAV9 | ||||
Spinal muscular atrophy | SMN2 | ABE | ~37% T > C correction | AAV9 | ||
Hypertrophic cardiomyopathy | Myh6 | ABE | ~32.3% A > G correction | AAV9 | ||
ABE | ~32.3% A > G correction of DNA | AAV9 | ||||
Ornithine transcarbamylase deficiency | OTC | Cas9-HDR | ~10% A > G correction | AAV8 | ||
Cas9-HDR | ~6% OTC cDNA insertion | AAV8 | ||||
Familial Hypercholesterolemia | LDLR | Cas9-HDR | ~6.7% T > G correction | AAV8 | ||
Fabry disease | GLA | ZFNs-HDR | ~1.7% human GLA cDNA insertion | AAV8 | ||
Adrenoleukodystrophy | ABCD1 | HITI | Human ABCD1 insertion | AAV9 | ||
phenylketonuria | PAH | CBE | 21.9–26.9% C > T correction | AAV8 | ||
PE | 2.0%–6.9% C > T correction | AdV | ||||
Type I tyrosinemia | FAH | Cas9-HDR | ~9% A > G correction | Plasmid | ||
ABE | ~9.5% A > G correction | Plasmid | ||||
PE | ~11.5% A > G correction | Plasmid | ||||
PE | ~0.76% 1.3 kb deletion and 19 bp insertion of hepatocytes | Plasmid | ||||
Hutchinson-Gilford progeria syndrome | LMNA | ABE | 20%–60% T > C correction | AAV9 | ||
Inherited retinal disease | RPE65 | ABE | ~16% T > C correction | Lentivirus | ||
ABE | ~22% T > C correction | AAV2 | ||||
PE | ~6.8% T > C correction | AAV8 | ||||
PE | ~11.4 T > C correction | AAV8 | ||||
Atherosclerotic cardiovascular disease | PCSK9 | ABE | ~50% A > G conversion | AAV8 | ||
ABE | ~60% A > G conversion | LNP | ||||
Ischemia/reperfusion injury | CaMKIIδ | ABE | 7.6% A > G conversion | AAV9 |
