h09 — Synthetic Peptide Hydrogel HTC

mech. Self-assembling peptide (SAP, ~134 aa tail91 on RADA16-WH2 scaffold) forms synthetic horizontal top connectors; engages TMEM145 GOLD zone (ipTM 0.68) + G-actin (ipTM 0.51). delivery. Ototopical ear drop + LIFU round-window permeation; PKPD window 0.13-1.32 mg; $42/ear GMP via NCL. patient-fit. Works on any STRC-null including Misha; peptide wins vs maternal E1659A at 1-10 µM in 10/12 Kd scenarios.

status

S-tier as of STRC h09 Phase 4m Kd Mono Soft Floor Result 2026-04-27. The dominant Kd_mono uncertainty from Phase 4n now has a preregistered soft-floor PASS: h09 WH2 predicts Kd_F=1.48 mM, which closes the Phase 4j conservative avidity gate.

Phase 4k supporting audit is complete: tandem proxies produce geometric contacts, but no confidence-supported WH2-actin contacts. Treat it as an AF3 short-motif caution, not as the gate-closing evidence.

Current follow-up:

1. Work through STRC h09 Reviewer Pack Queue 2026-04-27.
2. Leave Phase 4l optional unless a reviewer needs paper-grade C_eff.

Recent activity

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• h09 log
• strc
• h09
• Reviewer pack completed. STRC h09 Precedent Table Placeholder 2026-04-27, STRC h09 Orthogonal WH2 Controls Placeholder 2026-04-27, and STRC h09 Transfer Memo Placeholder 2026-04-27 drafted. Phase 4p Boltz-2 orthogonal WH2 panel completed 9/9 on M5 Max MPS: h09 WH2 ipTM=0.706, all negatives lower, verdict PASS-supportive; WIP false-low and Tbeta4 false-high keep it reviewer-support only. Ranking delta: S held; mech 5 / deliv 4 / misha_fit 3 unchanged. → STRC h09 Phase 4p Boltz WH2 Orthogonal Controls 2026-04-27
• Reviewer premortem drafted. STRC h09 Reviewer Premortem Placeholder 2026-04-27 now states the hostile-read objections, current answer, residual risk, and minimum next check before external review. Ranking delta: S held; mech 5 / deliv 4 / misha_fit 3 unchanged; reviewer-pack prose does not move tier.

evidence

• STRC Synthetic Peptide Hydrogel HTC — main hypothesis
• STRC Hydrogel HTC Phase 1 Self-Assembly — Phase 1-3b: analytical pre-screen → AF3 retool → full-construct validation
• STRC Hydrogel Phase 4 Computational Campaign — 8-axis campaign: 4a-4h all complete except 4b AF3 batch

scripts

models/ (legacy pool — see STRC Computational Scripts Inventory § Hypothesis 1, h09-specific rows)

• hydrogel_phase1_self_assembly.py
• af3_jobs_2026-04-23b_hydrogel_builder.py through af3_jobs_2026-04-23f_hydrogel_phase4b_builder.py (4 builders)
• hydrogel_phase4a_cif_interface_forensics.py through hydrogel_phase4h_endogenous_strc_competition.py (8 scripts)
• hydrogel_phase4c_sequence_liabilities.py — tail91_v2 Cys→Ser variant design

log

h09 log

cross

• STRC Mini-STRC Single-Vector Hypothesis — h03 is primary AAV path; h09 is independent materials path
• STRC Engineered Homodimer Avidity — h26 strengthens h03; h09 is parallel non-AAV track

Connections

• [part-of] STRC Hypothesis Ranking
• [about] Misha