Table 1.

A Summary of Successful Studies Using AAV-Based Gene Therapy to Target Proteostasis Alterations in Preclinical Models of Disease

Organ	Disease/Condition	Vehicle	Administration/Target	Phenotype	References
Eye	glaucoma	AAV2-XBP1s	intravitreal	increases neuronal survival	Hu et al.84
	MS/optic neuritis	AAV2-XBP1s in chop KO context	intravitreal	preserved visual function	Huang et al.85
	optic nerve crush	AAV2-Hsp70	intravitreal	increased retinal ganglion cells	Kwong et al.118
	retinal degeneration	AAV2-XBP1s	intravitreal	reduces axonal degeneration	Hu et al.84
	retinitis pigmentosa	AAV5-BiP	sub-retinal	restores visual function in mutant rhodopsin transgenic rats	Gorbatyuk et al.83
Heart	myocardial ischemia/reperfusion	AAV9-ATF6f	i.v.	decreased injury and improved function	Jin et al.91
CNS	amyotrophic lateral sclerosis	AAV6-SIL1	i.c.v.	delayed muscle denervation and prolonged survival	Filézac de L’Etang et al.70
	Huntington’s disease	AAV2-XBP1s	striatum	reduces aggregation of mutant huntingtin	Zuleta et al.72
	memory	AAV6-XBP1s	hippocampus	increased learning and memory	Martinez et al.61
	Parkinson’s disease	AAV5-BiP	SNpc	reduces toxicity and aggregation of α-synuclein	Gorbatyuk et al.54
		AAV2-XBP1s	SNpc	protected dopaminergic neurons and reduces striatal denervation against 6-OHDA	Valdes et al.52
		AAV6-Rab1A	SNpc	motor improvement	Coune et al.56
	spinal cord injury	AAV2-XBP1s	T12-13 level	improves locomotor recovery	Valenzuela et al.76
PNS	sciatic nerve injury	AAV2-XBP1s	DRG	enhanced axonal regeneration	Onate et al.78

6-OHDA, 6-hydroxydopamine; AAV, adeno-associated virus; BiP, binding immunoglobulin protein; CHOP, C/EBP homologous protein; DRG, dorsal root ganglia; HSP70, heat shock protein 70; i.c.v., intracerebroventricular; i.v., intravenous; MS, multiple sclerosis; PNS, peripheral nervous system; Rab1A, Rab GTPase 1A; SIL1, SIL1 nucleotide exchange factor 1; SNpc, substantia nigra pars compacta; XBP1s, X-box binding protein 1 (spliced form).