Table 4.

Adverse effects and toxicities resulting from rAAV administration

Toxicity	Pathology	Proposed mechanism	Supportive Treatment	Possible Association
Genotoxicity	Tumorigenesis identified in animals but unknown in humans	DNA damage	Unknown	rAAV serotype, promoter/enhancer elements, vector purities
Hepatotoxicity	• Liver enzyme elevation	• DNA damage	Corticosteroids	i.v., dose
Hepatotoxicity	• Drug-induced liver injury (rare)	• ER stress	Corticosteroids	i.v., dose
Thrombotic microangiopathy	• Endothelial vessel injury	Complement activation	• Corticosteroids	i.v., dose
	• Microvascular thrombosis		• Complement inhibition
	• Microvascular thrombosis		• Plasmapheresis
Dorsal root ganglion	• Immune cell infiltrates	Cellular overload with transgene	Unknown	c.m., i.t., dose
Dorsal root ganglion	• Nerve cell body degeneration	Cellular overload with transgene	Unknown	c.m., i.t., dose
Brain MRI findings	• Edema/inflammation	Unknown	Unknown	i.t., i.p., clinical significance unclear
	• Gliosis
	• Immune cell infiltrates

ER endoplasmic reticulum, i.v. intravenous, c.m. cisterna magna, i.t. intrathecal, i.p. intraparenchymal