Table 1.

Factors potentially impacting biological activity of AAVs in clinical use.

Product	Vector/origin	Transgene	Promoter	Enhancer	Tissue tropism (based on clinical use) (33)
Glybera	AAV1 (NHP)	hLPL	CMV/IEP	WPRE	CNS, muscle, heart; WPRE increases expression level of hLPL
Luxturna	AAV2 (human)	hRPE65	CMV/CBA	none	Liver, CNS, muscle, eye
Zolgensma	AAV9 (NHP)	hSMN1	CMV/CBA	none	Wide tropism, AAV9 can penetrate the blood brain barrier and drive gene expression throughout the CNS
Upstaza	AAV2 (human)	hAADC	CMV/IEP	HBG2/3	Liver, kidney, retina; truncated HBG2/3 increases expression of the transgene
Roctavian	AAV5 (human)	hFVIII	LSP	none	CNS, lung, eye
Hemgenix	AAV5 (human)	hFIX	LSP	none	CNS, lung, eye

NHP, non-human primate; hLPL, human lipoprotein lipase; hRPE65, human retinal pigment epithelium 65 kDa protein producing gene; hSMN1, human survival motor neuron 1 gene; hAADC, human aromatic L-amino acid decarboxylase gene; hFVIII, human coagulation factor VIII; hFIX, human coagulation factor IX; CMV/EIP, Cytomegalovirus early immediate promoter; CMV/CBA, Cytomegalovirus enhancer/chicken-β-actin hybrid promoter; LSP, liver specific promoter; WPRE, Woodchuck hepatitis virus post-transcriptional regulatory element; HBG2/3, human b-globin partial intron 2/partial exon3; CNS, central nervous system.