Table 1.
Viral vectors for inner ear gene therapy
| Viral vector | Transgene | Animal | Route | Tropism | Side Effects | Reference |
|---|---|---|---|---|---|---|
| Adenovirus | ||||||
| Ad5 | GFP | Mouse (adult) | RW | Cochlear and vestibular hair cells | Inflammatory response | [98] |
| Ad5 (E1A-, E1B-) | lacZ | Guinea pig (adult) | RW | Spiral ganglion neurons, cochlear supporting cells and connective tissue | Mild inflammatory response | [99] |
| Ad (E1-) | β-gal | Rat (neonatal) | In vitro | Organ of Corti, spiral ganglion neurons | No signs of cellular damage reported | [100] |
| Ad (E1-, E3-, CMV) | GFP | Rat (adult) | Peri- and endolymphatic perfusion | Mesothelial cells of scala media (i.e. Reissner’s membrane); Hensen’s, Deiters’, pillar and phalangeal cells; satellite cells surrounding SGN | Increased compound action potential (CAP) threshold | [101] |
| Coch | Cochlear inner and outer hair cells (in 2/6 animals) | Increased CAP threshold | ||||
| Ad (E1-, E3-, pol-) | GFP | Guinea pig (adult) | RW | Cochlear inner hair cell and pillar cells | Loss of DPOAE | [102] |
| Ad (E1-, E3-, pol-) | GFP-BDNF GFP-NT3 | Guinea pig (adult) | Coch | Inner and outer pillar cells, Deiters’ cells, Hansen’s cell, inner sulcus cells and interdental cells | Mild to moderate fibrosis and new bone growth | [103] |
| Ad | GFP-Kir2.1 | Mouse (neonate) | In vitro | Vestibular hair cells | No evidence of toxicity | [104] |
| AAV | ||||||
| AAV2/1 | GFP | Mouse (Embryonic) | Trans-uterine | Cochlear progenitor cells, which gave rise to inner and outer hair cells and supporting cells | No adverse effects found | [105] |
| AAV1 | GFP | Mouse (neonate) | Coch | Inner hair cells, cochlear supporting cells and lateral wall | Hearing loss reported when injected into scala media | [106] |
| AAV2 | dXIAP | Rat (adult) | RW | Spiral ganglion and stria vascularis | None reported | [107] |
| AAV1 | VGLUT3 | Mouse (juvenile) | RW or Coch | Inner hair cells | None reported | [108] |
| AAV8 | Whirlin | Mouse (neonatal) | RW | Inner hair cells and some outer hair cells | None reported | [109] |
| Mouse (adult) | RW | Inner hair cells (low efficacy) | ||||
| AAV8 | Whirlin | Mouse (neonatal) | PSSC | Vestibular hair cells and cochlear inner hair cells | None reported | [110] |
| AAV8 | Neurotrophin-3 | Guinea pig (adult) | Coch | Inner hair cells | None reported | [111] |
| Anc80L65 | GFP | Mouse (neonatal) | RW | Inner and outer hair cells, spiral ganglion neurons, cochlear supporting cells | No adverse effects on hair cell or hearing function | [112] |
| Human | In vitro | Vestibular hair cells and supporting cells | ||||
| AAV8 | Sans-IRES-GFP | Mouse (neonate) | RW | Vestibular and cochlear hair cells | None reported | [113] |
| AAV2/Anc80L65 | GFP | Mouse (adult) | PSSC | Cochlear hair cells, interdental cells, Reissner’s membrane, spiral limbus. Vestibular hair cells and supporting cells and vestibular ganglion cells | No adverse effects on hair cell or hearing function | [114] |
| Herpes Simplex virus | lacZ | Guinea pig (adult) | RW | Supporting cells, epithelial and connective tissues of cochlea. | Inflammatory response | [115] |
| NT-3myc | Mouse (neonatal) | In vitro | Spiral ganglion | None reported | [116] | |
RW-round window
PSSC-posterior semicircular canal
Coch-Cochleostomy
AAV - adeno-associated virus