h03 log
2026-04-23
- Misha compound-het stack integration: S held, scores unchanged, endpoint framing clarified. h03 for Misha’s specific genotype is physically ceiling-capped at MILD (~30-40 dB ABR) — at realistic transduction ε ≤ 0.5, ≥50% of OHCs remain non-transduced and cannot be rescued by AAV (maternal E1659A sub-threshold + paternal null → f_OHC < θ). “Meaningful rescue” endpoint intact (20-30 dB ABR improvement vs 64 dB baseline is clinically huge and matches OTOF trial responder criteria). “Cure” endpoint (NORMAL ≤ 25 dB) requires h01 co-therapy. No compute work needed on h03; this is endpoint semantics. → Misha Compound-Het Therapy Stack Model
- S-tier reinforced: AAV-LNP stack model formalises AAV as primary path → STRC AAV-LNP Stack PKPD
2026-04-22
- S-tier reinforced: Iranfar 2026 CTM + Holt 2021 Science Advances + Regeneron AAV.104 → STRC Gene Therapy Landscape 2026
2026-04-21
- Delivery 4→5 confirmed: all 3 AF3 gates closed (GOLD 0.68, homodimer, TMEM145 0.43) → STRC Mini-STRC Truncation Interface Validation
- Mech 4→5: Ultra-Mini sub-Å RMSD at TMEM145; unlocks 2.6 kb AAV headroom → STRC Mini-STRC Truncation Interface Validation
- 0 CpG CDS at 3.65% CAI; clinical CDS ready → STRC Ultra-Mini CpG Depletion
- B8+WPRE3-compact vector architecture locked; Ultra-Mini-enabled only → STRC Ultra-Mini Promoter Shortlist
- Full-vector CpG audit: 48 CpG / 13.9 per kb, 67% from ITRs (irreducible floor) → STRC Ultra-Mini CpG Depletion
- Weak homodimer: real weak dimerization surface at ARM 1579-1581 (not AF3 artifact) → STRC Homodimer Interface From CIF
Connections
[part-of]h03 hub