Table 6.
Different AAVs for Transducing NHP or Human Inner Ear Cells.
| Treatment reagent | Research objective | Delivery route | Animal model | Virus volume and dosage | Transduction efficiency |
|---|---|---|---|---|---|
|
AAV9‐PHP.B‐GFP |
Verification of HC transduction | RWM | Macaque |
10µL High‐dose: 3 × 1011VG, Low‐dose: 1 × 1011VG |
High‐dose: ≈92% in IHC/OHCs, Low‐dose: No obvious transduction in HCs.[ 66 ] |
| Preclinical testing of transgenic expression in NHP cochlea | RWM | Cynomolgus monkeys (Macaca fascicularis) |
10/20 µL Low‐dose: 1 × 1011VG Middle‐dose: 2 × 1011VG High‐dose: 3.5/7 × 1011VG |
High‐dose: Almost 100% transduction in IHCs /OHCs Middle‐dose: ≈50% in IHC, ≈65% in OHC, Low‐dose: Almost 0% in HCs.[ 107 ] |
|
| Transduction verification of fetal and adult inner ear implants | Explant culture method | Adult human vestibular organs, fetal human inner ear |
18 µL 3.5 × 1012VG |
54‐62% and 42–80% eGFP+ HCs in adult ampulla and utricle, 22‐52% and 53–69% eGFP+ HCs in fetal cochlear and utricular samples.[ 108 ] | |
| AAV‐S‐EGFP | Proof of efficient NHP inner ear expression vector | RWM | Cynomolgus monkeys (Macaca fascicularis) |
20 µL High‐dose:5.8/4.7 × 1011VG Low‐dose: 8 × 1010VG |
High‐dose: Almost all types of cochlear cells are completely transduced, including 100% of IHCs, and 30%100% of OHCs, Low‐dose: The transduction efficiency of all cells in the cochlea was greatly reduced.[ 57 ] |
|
AAV1/Anc80L65 ‐eGFP |
Efficiency verification of carrier delivery in NHPs | RWM | Rhesus macaque |
30 µL 2.55 × 1011VG |
Anc80L65:Transduced 90% of the IHCs in the apical turn of the cochlea, AAV1:A downward trend transduction from the apex to the base.[ 109 ] |
| AAV1‐GFP | Clinical validation of the efficacy and safety of AAV1 in NHPs | RWM | Macaca fascicularis |
20 µL High‐dose: 2.5 × 1011VG, Low‐dose: 1.5 × 1011VG |
High‐dose: 63.16‐93.75% in IHCs; 27.78‐49.58% in OHCs, Low‐dose: 61.54‐87.5% in IHCs; 24.24‐61.54% in OHCs.[ 6 ] |
| Anc80L65‐EGFP | HC specific transfection | RWM | Cynomolgus monkeys |
20‐40 µL / |
Anc80L65‐Cmv‐EGFP: HCs and other inner ear cells, Anc80L65‐Myo15‐EGFP: only HCs.[ 5 ] |
VG: vector genomes, HC: hair cell, IHC: inner hair cell, OHC: outer hair cell, RWM: round window membrane.