Table 1.

Examples of therapeutic in vivo base editing and prime editing

Disease model	Key organ (cell type)	Editing outcome	Editor variant	Delivery method	Publication date	Reference
Hypercholesterolemia in mice	liver (hepatocytes)	28% editing, reduced PCSK9 protein expression	BE3	adenovirus	September 2017	175
Hypercholesterolemia in mice expressing human PCSK9	liver (hepatocytes)	∼20% editing, reduced PCSK9 protein expression	BE3	adenovirus	January 2019	176
Hypercholesterolemia in mice and macaque	liver (hepatocytes)	67% editing in mouse and 28% editing in macaque, reduced PCSK9 protein expression	ABE7.10max	AAV8 and LNP encapsulating mRNA	May 2021	177
Hypercholesterolemia in mice and macaque	liver (hepatocytes)	70% editing in mouse and 67% editing in macaque, reduced PCSK9 protein expression	ABE8.8 m	LNP encapsulating mRNA	May 2021	178
Hypercholesterolemia in mice	liver (hepatocytes)	30% editing in mouse, reduced PCSK9 protein expression	tBE-V5-mA3	AAV8	May 2021	108
Phenylketonuria in mice	liver (hepatocytes)	10% editing after 4 weeks increasing to 25% after 26 weeks. Return of blood phenylalanine to normal levels.	SaKKH-BE3	AAV8	October 2018	179
Phenylketonuria in mice	liver (hepatocytes)	23% editing after 8 weeks using AAV. 19% editing 1 week after second LNP dose. Return of blood phenylalanine to normal levels.	SaKKH-BE3	AAV8 and LNP encapsulating mRNA	February 2021	180
Phenylketonuria in mice	liver (hepatocytes)	10% editing using adenovirus to deliver PE3 to neonates. 2% editing when delivering PE2 to 5-week-old animals. <1% editing using AAV	PE2/PE3 lacking reverse transcriptase RNase H domain	AAV8 and adenovirus	August 2021	181
Tyrosinemia in mice	liver (hepatocytes)	9.5% editing and restoration of mouse body weight	optimized ABE6.3	hydrodynamic injection of DNA	February 2019	167
Tyrosinemia in mice	liver (hepatocytes)	12.5% editing and restoration of mouse body weight	optimized ABE6.3	LNP encapsulating mRNA	April 2020	182
Alpha-1 antitrypsin deficiency in mice expressing human SERPINA1	liver (hepatocytes)	6.7% correction by hydrodynamic injection, 3% correction by dual AAV 10 weeks after treatment	improved PE3	hydrodynamic injection of DNA and AAV8	April 2021	118
Hutchinson-Gilford progeria syndrome in mice expressing human progerin	heart (vascular smooth muscle cells)	30% editing in heart, 20% in aorta. 2.4-fold increase in lifespan.	ABE7.10max-VRQR	AAV9	January 2021	183
Duchenne muscular dystrophy in mice	skeletal muscle (myofibers)	3.3% local editing, 17% of local myofibers staining for restored dystrophin	ABE7.10	AAV9	April 2018	184
Duchenne muscular dystrophy in mice	skeletal muscle (myofibers)	35% local editing, 96% of local myofibers staining for restored dystrophin	ABE7.10max	AAV9	April 2021	185
Amyotrophic lateral sclerosis in mice harboring human SOD1-G93A	central nervous system (motor neurons)	1.2% editing frequency, 11% increase in lifetime and 85% increase in duration between onset of late-stage disease and death	BE3	AAV9	January 2020	186
Niemann-Pick disease in mice	central nervous system (Purkinje cells)	48% editing in cortex, 42% in Purkinje cells, up to 59% in cortex at test site. 10% increase in lifetime.	BE3.9max	AAV9	January 2020	187
Leber congenital amaurosis	retina (retinal pigmented epithelium)	15% base editing, restored visual function	ABE7.10max	lentivirus	October 2020	188
Leber congenital amaurosis	retina (retinal pigmented epithelium)	14% base editing, restored visual function. 89% editing in Rpe65 cDNA	ABE7.10max-SpCas9-NG	AAV9	January 2021	189
Recessive hearing loss in mice	inner ear (hair cells)	2.3% bulk genomic correction, 33% cDNA correction. Greatly increased hearing at 4 weeks that slowly degenerated	AID-BE3.9max	AAV (Anc80 serotype)	June 2020	190
Sickle cell disease/β-thalassemia in mice expressing human β-globin	blood (hematopoietic stem cells)	30% editing following selection, 21% of blood β-like globins were fetal hemoglobin	ABE7.10max	adenovirus	February 2021	191