Table 2.

AAV dose and serotypes used for systemic treatment in clinical trials

Gene therapy names	Disease	Gene to be delivered	AAV serotype	AAV dose (vg/kg)	Age and delivery route	Remarks	Clinical trials	Year	Sponsor/manufacture	Ref
Hemophilia
scAAV2/8-LP1-hFIXco	Hemophilia B	hFIXco	AAV8	2 × 1011, 6 × 1011, 2 × 1012	≥ 18 years, males; i.v. infusion	Confirmed efficacy and safety	NCT00979238; phase 1	2009	UCL, St Jude Children’s Res Hospital; Children’s GMP in Memphis	[9, 10, 19]
FLT180a	Hemophilia B	hFIXco	AAVS3	4.5 × 1011 7.5 × 1011 9.75 × 1011 1.5 × 012	≥ 18 years, males; i.v. infusion	Confirmed efficacy and safety	NCT03369444; phase 1	2017	UCL	[22]
AMT-060	Hemophilia B	hFIXco	AAV5	5 × 1012, 2 × 1013	≥ 18 years, males; i.v. infusion	Confirmed efficacy and safety	NCT02396342; EudraCT2013-005579-42; phase 1/2	2015	UniQure	[20]
AMT-061	Hemophilia B	hFIXco-Padua	AAV5	2 × 1013	≥ 18 years, males; i.v. infusion	Confirmed efficacy and safety	NCT03489291; phase 2 NCT03569891; phase 3	2018	UniQure	[22, 37]
SPK-9001	Hemophilia B	hFIXco-Padua	AAV8	5 × 1011	≥ 18 years, males; i.v. infusion	Confirmed efficacy and safety	NCT02484092; phase 1/2	2015	Spark Therapeutics and Pfizer	[21]
AAV-Spark100; SB-525	Hemophilia B; Hemophilia A	hFIXco-Padua; BDD-FVIII	AAV6	n.a.	18–64 years, males; i.v. infusion	n.a.	NCT03587116; phase 3	2018	Pfizer	n.a.
BMN270 (AAV5-hFVIII-SQ)	Hemophilia A	BDD-FVIII	AAV5	6 × 1012, 2 × 1013, 4 × 1013, 6 × 1013,	≥ 18 years, males; i.v. infusion	Confirmed efficacy and safety	NCT02576795, EudraCT2014-003880-38 Phase 1/2	2015;	BioMarin	[23]
BMN 270-301	Hemophilia A	BDD-FVIII	AAV5	6 × 1013	≥ 18 years, males; i.v. infusion	Confirmed efficacy and safety	NCT03370913, phase 3	2017	BioMarin	[38]
BMN270-302	Hemophilia A	BDD-FVIII	AAV5	4 × 1013	≥ 18 years, males; i.v. infusion	n.a.	NCT03392974; phase 3	2018	BioMarin	n.a
SPK-8011	Hemophilia A	BDD-FVIII	AAV-LK03	5 × 1011, 1 × 1012, 2 × 1012	≥ 18 years, males; i.v. infusion	Confirmed efficacy and safety	NCT03003533; phase 1/2	2016	Spark Therapeutics	[24]
PF-07055480	Hemophilia A	BDD-FVIII	AAV6	3 × 1013	18–64 years, males; i.v. infusion	Confirmed efficacy and safety	NCT04370054; phase 3	2020	Pfizer	[39]
Spinal muscular atrophy (SMA)
Zolgensma (AVXS-101)	SMA	SMN	AAV9	6.7 × 1013; 2 × 1014	≤ 6 months i.v. infusion	Confirmed efficacy and safety FDA approved	NCT02122952; phase 1	2014	AveXis,	[15]
Zolgensma (AVXS-101)	SMA	SMN	AAV9	n.a.	≤ 6 months i.v. infusion	Confirmed efficacy and safety FDA approved	NCT03306277; phase 3 NCT03461289; phase 3	2017; 2018	AveXis,	[40, 41]
Zolgensma (AVXS-101)	SMA	SMN	AAV9	n.a.	≤ 6 months i.v. infusion	n.a.	NCT03837184; phase 3	2019	Novartis	n.a
Zolgensma (AVXS-101)	SMA	SMN	AAV9	1.1 × 1014	≤ 42 days i.v. infusion	Confirmed efficacy and safety FDA approved	NCT03505099; phase 3	2018	Novartis	[42]
Systemic treatment for other inherited diseases
BMN 307	PKU	PAH	n.a.	3 dose levels not disclosed	≥ 15 years, i.v. infusion	n.a.	NCT04480567; phase 1/2	2020	BioMarin	n.a
HMI-102	PKU	PAH	AAVHSC15	3 dose levels not disclosed	18–55 years, i.v. infusion	n.a.	NCT03952156; phase 1/2	2019	Homology Medicines,	n.a
DTX301 (scAAV8OTC)	OTC deficiency	OTC	AAV8	2 × 1012; 6 × 1012; 1 × 1013	≥ 18 years, i.v. infusion	n.a.	NCT02991144; phase 1/2	2016	Ultragenyx	n.a
GNT0003	Crigler-Najjar syndrome	UGT1A1	AAV8	2 dose levels not disclosed	≥ 9 years, i.v. infusion	n.a.	NCT03466463; phase 1/2	2018	Genethon	n.a
AAV-hLDLR	Familial hypercholesterolemia	LDLR	AAV8	n.a.	≥ 18 years, i.v. infusion	n.a.	NCT02651675; phase 1/2	2016	Regenxbio	n.a
DTX401	GSD1a	G6PC	AAV8	3 dose levels not disclosed	≥ 18 years, i.v. infusion	n.a.	NCT03517085; phase 1/2	2018	Ultragenyx	[43]
ABO-102 (scAAV9.U1a.hSGSH)	MPS IIIA	SGSH	AAV9	0.5 × 1013 1 × 1013 3 × 1013	≥ 6 months, i.v. infusion	Signs of efficacy	NCT02716246; phase 1/2 NCT04360265 (follow-up)	2016; 2020	Abeona Therapeutics	[44]
AT132	X-linked myotubular myopathy	hMTM1	AAV8	1 × 1014 3 × 1014	≤ 5 years, males; i.v. infusion	Confirmed efficacy and safety for the low-dose group; three deaths from the high-dose group	NCT03199469; phase 1/2	2017	Audentes Therapeutics	[35]