Base Editing Cochlear Precedent 2024
August 2024: ABE7.10max + SpCas9-NG delivered via dual AAV, injected through the round window membrane in mice. Corrected a pathogenic OTOF mutation. 88% of inner hair cells expressed normal otoferlin. Hearing restored to near-wild-type levels. Stable for more than 1.5 years.
That last part is critical. 1.5 years of stable correction in a post-mitotic cell. No degradation. The edit sticks.
October 2024: PAM-flexible ABE variants rescued hearing in a humanized MPZL2 mouse model carrying an East Asian founder mutation. Another proof point for base editing in the cochlea.
For STRC E1659A: Base editors can’t fix our variant. It’s a transversion (C>A). Adenine base editors do A-to-G transitions. Cytosine base editors do C-to-T. Neither handles C-to-A. So base editing is off the table for Misha’s specific mutation.
But the precedent is what counts here. If ABE works in cochlea (and it clearly does, with 88% efficiency and 1.5-year durability), then prime editing should work too, once the delivery problem is solved. Prime editors are larger, harder to package, but the cochlear environment itself isn’t the bottleneck. The cells accept the edits. The edits persist.
This strengthens the prime editing hypothesis for STRC.
Connections
- STRC Gene Therapy — base editing precedent supports prime editing path
- Prime Editing for STRC — cochlear feasibility evidence
- STRC Variant c.4976A>C — Misha — base editing can’t fix this specific variant
- STRC E1659A Conservation and Reclassification — variant classification context
- Alternative STRC Delivery Hypotheses — delivery remains the bottleneck