Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate
In macaque, Anc80L65 via round window transduced 90-30% of inner hair cells but only four outer hair cells in total — the OHC gap that h03 delivery depends on.
Citation
Andres-Mateos E, Landegger LD, Unzu C, Phillips J, Lin BM, Dewyer NA, et al. “Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate.” Nature Communications 13:1359, 2022. DOI 10.1038/s41467-022-28969-3. Open access, PMC8924271.
What they found
AAV-Anc80L65 delivered to the macaque cochlea by transmastoid facial recess exposure with round-window injection and oval-window venting achieves high, apex-to-base-graded transduction of inner hair cells, substantially outperforming AAV1 at equal dose. Outer hair cell transduction was effectively absent — reported not as a percentage but as individual counted cells.
The paper is the direct primate test of the vector and route that h03 relies on. Its own title names the surgical approach as a co-equal variable with vector choice, so the OHC result should be read as specific to this vector/route pairing rather than as a statement about the primate cochlea in general.
Numbers that matter
| Parameter | Value | Units | Source locator | Uncertainty |
|---|---|---|---|---|
| Dose administered (all animals) | 2.5e11 | vector genome copies in 30 µL | Results, methods statement | fixed, single dose — no dose-response reported |
| Anc80L65 IHC transduction, apical | up to 90 | % | Results | n = 2 animals |
| Anc80L65 IHC transduction, across cochlea | 90 → 30 | % (apex → base) | Results | gradient |
| AAV1 IHC transduction, across cochlea | 30 → 5 | % | Results | comparator at equal dose |
| Anc80L65 OHC transduction | 4 cells total | absolute count | Results | 1 cell at 32.0 kHz (ear RA3009); 3 cells at 22.6 kHz (ear RA3128) |
Verbatim, load-bearing:
only minimal outer hair cell (OHC) transduction was observed for both serotypes … Specifically, one positive outer hair cell was detected in the 32.0 kHz region of ear RA3009 and three appeared in the 22.6 kHz region of ear RA3128.
Anc80L65 in 2 animals transduced up to 90% of apical inner hair cells
Unlike rodent models, the NHP cochlea has similar anatomy and proportions to humans.
Why this matters for STRC
STRC/stereocilin is an outer hair cell protein. The OTOF clinical precedent frequently cited in support of h03’s deliv: 5 is an inner hair cell precedent — otoferlin is an IHC protein — so it evidences IHC transduction only. This paper is the primate test of the same vector by the same route for the cell type STRC actually needs, and the answer is four cells.
This does not kill h03. Dose here is a single 2.5e11 GC administration; surgical route is a named variable; n = 2 animals; and a negative OHC count can be assay-sensitive. What it does do is withdraw the basis for deliv: 5.
Recorded because it cuts against the program’s interest.
Connections
[applies]h03 hub[contradicts]the use of OTOF-trial transduction figures as evidence for outer hair cell delivery[see-also]2026-01-iranfar-dual-aav-strc-ctm — the mouse DFNB16 rescue reaching ~55-59% of OHCs with dual AAV9-PHP.eB[contradicts]2017-landegger-anc80l65-inner-ear-nbt — the P1-mouse 60-100% OHC figure this vault has quoted; same vector, same route, opposite OHC result in primate[see-also]Omichi_2020_AAV_hair_cell_transduction[part-of]STRC Cure-Route Audit 2026-08-20 — closes the “nosources/lit/note behind the Anc80L65 figures” gap that audit filed