Table 3.

Precise genome-editing-mediated gene therapy

Environment	Disease type	Target	Strategies	Editing efficiency	Delivery	References
Ex vivo	Sickle cell disease	HBB	ZFN-HDR	~18% T > A correction	Lentivirus and electroporation	392
			Cas9-HDR	20–30% T > A correction	AAV and electroporation	393,394
			ABE	40%–80% A > G correction	Electroporation	395
			PE	~27% T > A correction	Electroporation	386
	β-thalassemia	IVS1	ABE	~80% A > G correction	Electroporation	396
		BCL11A, HBB	CBE	~90% C > T correction of BCL11A, ~18.2 C > T correction of HBB	Electroporation	397
		BCL11A, HBG	ABE	~94.3% A > G correction of BCL11A, ~85.5% A > G correction of HBG	Electroporation	398
	X-linked chronic granulomatous disease	CYBB	ZFN-HDR	~7.1% CYBB cDNA insertion	AAV and electroporation	400
			Cas9-HDR	~21% T > C correction	Electroporation	399
	Lymphoblastic leukaemia	TRAC	Cas9-HDR	~46.5% CAR insertion of T cells	AAV6 and electroporation	407
	Glioblastoma	AAVS1	Cas9-HDR	>90% CAR insertion of cells	Nucleofection	408
In vivo	Duchenne muscular dystrophy	DMD	HITI	4% ~ 7% Exon 52 insertion	AAV9	284
			ABE	~51.0% A > G correction	AAV9	287
	Spinal muscular atrophy	SMN2	ABE	~37% T > C correction	AAV9	410
	Hypertrophic cardiomyopathy	Myh6	ABE	~32.3% A > G correction	AAV9	412
			ABE	~32.3% A > G correction of DNA	AAV9	412
	Ornithine transcarbamylase deficiency	OTC	Cas9-HDR	~10% A > G correction	AAV8	282
			Cas9-HDR	~6% OTC cDNA insertion	AAV8	413
	Familial Hypercholesterolemia	LDLR	Cas9-HDR	~6.7% T > G correction	AAV8	283
	Fabry disease	GLA	ZFNs-HDR	~1.7% human GLA cDNA insertion	AAV8	414
	Adrenoleukodystrophy	ABCD1	HITI	Human ABCD1 insertion	AAV9	286
	phenylketonuria	PAH	CBE	21.9–26.9% C > T correction	AAV8	109
			PE	2.0%–6.9% C > T correction	AdV	240
	Type I tyrosinemia	FAH	Cas9-HDR	~9% A > G correction	Plasmid	415
			ABE	~9.5% A > G correction	Plasmid	310
			PE	~11.5% A > G correction	Plasmid	417
			PE	~0.76% 1.3 kb deletion and 19 bp insertion of hepatocytes	Plasmid	416
	Hutchinson-Gilford progeria syndrome	LMNA	ABE	20%–60% T > C correction	AAV9	419
	Inherited retinal disease	RPE65	ABE	~16% T > C correction	Lentivirus	421
			ABE	~22% T > C correction	AAV2	422
			PE	~6.8% T > C correction	AAV8	417
			PE	~11.4 T > C correction	AAV8	420
	Atherosclerotic cardiovascular disease	PCSK9	ABE	~50% A > G conversion	AAV8	425
			ABE	~60% A > G conversion	LNP	426,427
	Ischemia/reperfusion injury	CaMKIIδ	ABE	7.6% A > G conversion	AAV9	430

ZFN zinc-finger nuclease, HDR homology-directed repair, HITI homology-independent target integration, ABE adenine base editor, CBE cytosine base editor, PE prime editor, AAV adeno-associated virus, AdV adenovirus, LNP lipid nanoparticles