Table 1.
The brief history of gene therapy in hearing diseases.
| Animal model | Treatment reagent | Injection time and delivery method | Ave. ABR improvement (best freq.) and treatment efficacy | Targeted cells and major morphological improvement |
|---|---|---|---|---|
| Vglut3−/− mice [2] | AAV1-Vglut3 |
P1–3 and P10 Route: AC and RWM |
~50 dB (90 dB of control) Lasted for 3–6 months |
IHCs/Improve the morphology of partial afferent IHC ribbon synapses. |
| Kcnq1−/− mice [54] | AAV1-Kcnq1 |
P0–2 Route: Scala media |
~45 dB (90 dB of control) Lasted for 4–6 months |
SV marginal cells/rescue the collapse of Reissner’s membrane death of HCs and cells in the SG. |
| MsrB3−/− mice [55] | AAV2/1-MsrB3 |
E12.5 Route: in utero |
~40–50 dB | IHCs and OHCs/recovery hearing and the morphology of the stereociliary bundles. |
| Slc26a4−/− and Slc26a4tm1Dontuh/ tm1Dontuh mice [56] | rAAV2/1-Slc26a4 |
E12.5 Route: in utero |
~20–40 dB(8–12 weeks) | IHCs, OHCs and stria vascularis/restored hearing phenotypes included normal hearing and progressive hearing loss. |
| Gjb2cKO mice Cx26fl/flP0-Cre [57] | AAV5-Cx26 |
P0 and P42 Route: RWM |
~20 dB in P0 (100 dB of control mice) ~0 dB in P42 |
IHC, OHCs, and SCs/rescue the formation of organ of Corti and HCs. No morphology change in P42. |
| Whrnwi/wi mice [58] | AAV2/8-whirilin |
P1–5 Route: PSC |
~20 dB Lasted for 4 months Rescue the vestibular function |
IHCs/rescue the morphology and function of stereociliary bundles and temporarily the death of IHCs. |
| Clrn1ex4/– mice [28] | AAV2/8-Clrn1 |
P1–P3 Route: RWM |
~30–40 dB | IHCs and OHCs/restored hearing phenotypes included normal hearing as well as the synaptic ribbons. |
| Clrn1–/–-TgAC1 mice [59] | AAV2/8-Clrn1 | P1–P3 Route: RWM |
~30–40 dB Lasted for 5 months |
IHCs and OHCs/restored the hair bundle structure and hearing. |
| Usher1c (c.216G>A) [29] | AAV2-harmonin |
P0–1 and P10–12 Route: RWM |
~50–60 dB (110 dB of control) Lasted for 6 months |
IHCs and OHCs/rescue the function of stereociliary bundles and death of HCs. |
| Otof−/− mice [21] | Dual AAV |
P10 and P17 and P30 Route: RWM |
~30–40 dB Lasted for 5–6 months |
IHCs/restore the number of ribbons by promoting their production. |
| Otof−/− mice [60] | Dual AAV2/6half-vector |
P6–7 Route: RWM |
~50–60 dB(110 dB of control) | IHCs/restore the exocytosis function of IHC and partially the number of ribbons. |
| TMC−/− mice [61] | AAV2/1-Cba-Tmc |
P0–2 Route: RWM |
~20–30 dB (110 dB of control) | IHCs and OHCs/restore the sensory transduction current of HCs, SCs, and SGs. |
| TMC−/− mice [62] | sAAV-Tmc1 |
P0–2 Route: RWM |
~50–60 dB (110 dB of control) Lasted for 3 months Rescue the vestibular function |
IHCs and OHCs/rescue the function of stereociliary bundles, sensory transduction current, and death of HCs. |
| Tmc1Bth/+ mice [63] | Cas9: gRNA |
P1 Route:Scala media |
~20–30 dB | IHCs and OHCs/rescue the death of HCs. |
| Tmc1Bth/+ mice [31] | rAAV2/9miTmc1 |
P0–2 Route: RWM |
~30–40 dB | IHCs and OHCs/rescue the number of IHCs and OHCs partially. |
| Tmc1Bth/+ mice [27] | AAV-SaCas9-KKH |
P1 Route: Scala media |
~30–40 dB | IHCs and OHCs/rescue the morphology of stereociliary bundles and the death of IHCs. |
| Tmc1Bth/+ mice3 | AAV9.miTmc1 |
P15–16 and P56–60 and P84–90 Route: RWM + SF |
~30–40 dB No difference in P84–90 |
IHCs, OHCs, and SV/rescue the morphology of stereociliary bundles and temporarily the death of IHCs. |
PSC posterior semicircular canal, AC apical cochleostomy, SF semicircular fenestration.