B-tier promotion triage: local reruns after post-split path fix confirmed no fast compute-to-S path. v2 OHC-tropism max cochlea-mean = 1.37x at aspirational 20% OHC-targeted; realistic 1-3% = 1.018-1.055x. AAV-LNP stack adds only 0.12-0.92% relative under realistic AAV 50-70% @5x. Tier B held; next_step reframed as maintenance/interim only pending new OHC-LNP coverage data. →STRC B-Tier Promotion Triage 2026-04-27
2026-04-25
#4 mRNA-LNP lit-audit closure (h06 inherits): Hill WARNING propagated to shared scripts. LNP OHC 20% confirmed aspirational — no primary paper shows ≥5% LNP-mRNA OHC efficiency; closest precedent Gao 2018 Nature (PMC5784267) ~0.92% indel in organ of Corti (lipid-RNP, not LNP-mRNA). Gao 2020 phantom confirmed absent from strc_mrna_strategy_b_pkpd.py. lit_audit → fixed. → STRC h06 Parameter Provenance Audit 2026-04-25
2026-04-23
#6 mRNA Therapy post-audit partial fix: A held. STRC_HL_D + RBM24_HL_D reframed from ⚠ UNSOURCED to lit-anchored OOM estimates (Zhang 2012 Nature PMID 22246323 for stereocilia <10 %/day; Mauriac 2024 PNAS PMID 39320919 for GPSM2 t½ 9–10 d; Schwanhäusser 2011 Nature PMID 21593866 for proteome median 46h). Hill K_M/n/max_boost stay CIRCULAR FIT (no OHC splicing dose-response lit exists). #4 Strategy B inherits. → STRC h06 Parameter Provenance Audit 2026-04-23
#4 Strategy B: S → B. Misha-fit 5→2. Stack PKPD: adds 0.12-0.92% cochlea-mean at realistic AAV. → STRC AAV-LNP Stack PKPD