Iranfar 2026 — Dual AAV STRC Gene Therapy (CTM)
Journal: Clinical and Translational Medicine, January 2026 (16, e70571)
DOI: 10.1002/ctm2.70571
PMC: PMC12784207
Link: https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70571
Lab: Christine Petit group, Institut Pasteur, Paris
PDF: ~/BookLibrary/incoming/Iranfar_2026_Dual-AAV-STRC-DFNB16-hearing-recovery_ClinTranslMed.pdf
Delivery: posterior semicircular canal injection, neonatal P0–P2 mouse
Key Ideas
- Dual AAV9-PHP.eB vectors deliver full-length STRC cDNA split at a shared recombinogenic sequence. STRC at 5,430 bp exceeds single-vector capacity; dual delivery reconstitutes full protein via recombination in OHCs.
- Restored stereocilin expression at OHC stereocilia tips in ~60% of cells. Horizontal top connectors and tectorial membrane attachment crowns rebuilt.
- Cochlear amplification and ABR thresholds recovered to normal. Frequency discrimination (gap detection behavioral assay) also restored.
- 60% OHC transduction drives full functional rescue, implying intercellular compensation — a clinically important threshold to know.
- Durability confirmed out to 100 days post-injection.
- Authors state explicit intent to move to human trials.
My Thoughts
This is the anchor paper for the STRC Gene Therapy Landscape 2026 note and the strongest external validation of the STRC Mini-STRC Single-Vector Hypothesis program. AAV9-PHP.eB outperformed AAV2, AAV8, and Anc80L65 in their comparative transduction screen — that’s a meaningful vector selection datum, though PHP.eB’s CNS tropism in humans is less proven than its mouse track record.
The 60% transduction → 100% functional rescue finding is the most actionable number for Misha’s family: the therapy doesn’t need to hit every OHC. That directly addresses the “what if some OHCs are already damaged” fear.
Dual-AAV efficiency (~60%) is lower than a single-vector could achieve. If STRC Mini-STRC Single-Vector Hypothesis works, it’s superior on this axis. The two programs are complementary, not competing — Pasteur’s work validates the target; Egor’s compute validates a potentially more efficient delivery.
Connections
[supports]STRC Mini-STRC Single-Vector Hypothesis — parallel academic validation of dual-AAV STRC approach[part-of]STRC Gene Therapy Landscape 2026[about]Misha[see-also]STRC DFNB16 Therapeutic Window Iranfar 2026[supports]Dual Vector AAV Strategy[applies]DFNB16 Hearing Loss[see-also]Omichi_2020_AAV_hair_cell_transduction — AAV serotype selection for OHC[see-also]Jeffrey Holt — STRC dual-AAV program, Boston Children’s/Harvard- Christine Petit — corresponding author, Institut Pasteur