Table 1.

Summary of viral vectors used for inner ear gene therapy

Vector	Serotype	Capacity	Targets	Advantages	Disadvantages	References
Lentiviruses: HIV-1, FIV	Pseudotypes with glycoproteins from vesicular stomatitis virus, measles virus, murine leukemia virus, adenovirus, and many others	Up to 8 kb	In vitro: spiral ganglion neurons, glial cells, supporting cells. In vivo: periphery of the perilymphatic space, scala tympani and scala vestibuli, marginal and intermediate cells of the stria vascularis, Hensen’s cells	Efficiently transduce both dividing and nondividing cells. Provide stable transgene expression in nondividing cells. Self-inactivating and integration-deficient vectors are available.	Minimal transduction of IHCs and OHCs. Possible ototoxic effects	Yang et al. (2013a), Bedrosian et al. (2006), Han et al. (1999), Pietola et al. (2008), Wei et al. (2013), Wang et al. (2013)
Adenoviruses (AdV)	AdV-2, AdV-5	1st generation: up to 7 kb 2nd generation: up to 14 kb 3rd generation: up to 36 kb	Cells lining the perilymphatic spaces and scala media, Hensen’s, Deiters’, pillar and phalangeal cells, satellite cells of the spiral ganglion neurons, hair cells	Efficiently transduce both dividing and nondividing cells. AdVs of 3rd generations may provide very long transgene expression	AdVs of 1st and 2nd generations can induce considerable immune response. Limited efficiency in hair cells	Zhang and Bergelson (2005), Husseman and Raphael (2009), Venail et al. (2006), Li Duan et al. (2002), Dazert et al. (1997), Kesser et al. (2007), Sacheli et al. (2013), Chien et al. (2015a, b), Yang et al. (2013b), Takada et al. (2015)
Adeno-associated viruses (AAV)	AAV1–8, pseudotyped AAVs, engineered AAVs-Anc80L65	Up to 4.8 kb	AAV1, 2, 4–7, 8: spiral limbus, spiral ligament, and spiral ganglion cells. AAV1, 2, 3, 5, 6, 8: IHCs. AAV5: Claudius cells, spiral ganglion, and inner sulcus cells. AAV2/1: progenitors of IHCs and OHCs. AAV2/2: IHCs. And80L65: IHCs and OHCs, type I and type II hair cells of the utricle and semicircular canals	Exceptionally long-term transgene expression. Safety and broad tropism to various cell types. Anc80L65 —exceptional efficient transduction of IHCs and OHCs	Limited packaging capacity requires additional techniques to deliver large transgenes	Jero et al. (2001), Li Duan et al. (2002), Liu et al. (2005), Kilpatrick et al. (2011), Chien et al. (2015), Bedrosian et al. (2006), Konishi et al. (2008a, b), Landegger et al. (2017)