Table 1.

Fatality cases following high-dose systemic AAV delivery

		Drug name	AAV				Clinical profile						Reference
			Serotype	Dose (vg/kg)	Promoter	Transgene	Disease	Patient age	Time of death	Cause of death	Immunotoxicity	Clinical trial ID
Acute death	PF-06939926		AAV9	2 × 1014	miniMCK	μDys gene	DMD	16 years	6 days post-dosing	heart failure	innate response	NCT03362502	Lek et al.,8 Philippidis9, and Lek et al.10
	CRD-TMH-001		AAV9	1 × 1014	CK8e	dCas9-VP64 and gRNA	DMD	27 years	8 days post-dosing	lung failure	innate response (cytokine-mediated)	NCT05514249	Lek et al.10
Subacute death	Zolgensma		AAV9	1.1 × 1014	CBA	SMN gene	SMA	≤2 years (4 patients)	5–6 weeks post-dosing	liver failure	adaptive response	post-marketing	Philippidis, Whiteley, and Kishimoto and Samulski6,19,20
	Zolgensma		AAV9	1.1 × 1014	CBA	SMN gene	SMA	6 months	8 weeks post-dosing	kidney failure	innate response (complement mediated)	post-marketing	Guillou et al.7
	AT132		AAV8	1.3–3 × 1014	DES	MTM1 gene	XLMTM	≤5 years (4 patients)	20–40 weeks post-dosing	liver failure	innate response?	NCT03199469	Shieh et al., Philippidis, Whiteley, and Kishimoto and Samulski4,5,19,20

miniMCK, CK8e, and DES are muscle-specific promoters. CBA is a ubiquitous promoter. μDys, microdystrophin; SMN, survival motor neuron; MTM1, myotubularin; DMD, Duchenne muscular dystrophy; SMA, spinal muscular atrophy; XLMTM, X-linked myotubular myopathy.