STRC Research

STRC Research

6 min read

STRC Research

Open research notebook on STRC gene therapy for DFNB16 hearing loss. Every hypothesis, proof, and literature note in one graph. Last updated 2026-04-25.

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Active Hypotheses (by tier)

TABLE WITHOUT ID
  hypothesis_num AS "#",
  file.link AS "Hub",
  tier AS "Tier",
  mech AS "Mech",
  deliv AS "Deliv",
  misha_fit AS "Misha",
  next_step AS "Next"
FROM "hypotheses"
WHERE type = "hypothesis-hub"
SORT tier ASC, hypothesis_num ASC
#HubTierMechDelivMishaNext
1indexA434Wetlab handoff packet v0.1 delivered 2026-04-27. H01 is ready for assay-scoping RFQ, not lead-candidate nomination. P0 next: send separate RFQs for (1) v5.3 custom synthesis of 1-indanyl_acylsulfonamide_SO2Me_-Cl + adamantyl_acylsulfonamide_SO2Me_-Cl, optional adamantyl_-CF3; (2) STRC 1066-1216 K1141-fragment WT/E1659A expression feasibility; (3) DSF/nanoDSF + SPR/BLI/MST direct-binding/stabilization cascade. Production holo MD/MM-PBSA remains paper-grade support, not wetlab-contact blocker. A held; mech 4 / deliv 3 / misha_fit 4 unchanged. A_hold_wetlab_rfq_feasibility. → STRC h01 Wetlab Handoff Packet 2026-04-27
4indexB322No fast compute-to-S path; keep as AAV maintenance/interim only unless new OHC-LNP tropism data reaches therapeutic population coverage
6indexB222No fast compute-to-S path; needs primary OHC RBM24 titration/Sun 2026 quantification before another model can change tier
10indexC222Wet-lab only if #3 fails
11indexC222Alt scaffold deferred
12indexC222Speculative; no near-term path
13indexC213Technology-watch only
14indexC213No delivery route
2indexC215Blocked on literature — V_saturation, OHC membrane resistance, 210 kPa Young’s modulus all unsourced; TM displacement 5–30 nm is in-house assumption. No compute advance until primary lit retrieved.
26indexC254Paused: Phase 1d A1078C/S1080C/S1579C/A1078W all fail AF3 G1; no further compute unless a new scaffold/interface appears
27indexC224Email Holt lab ribosome-profiling
5indexC342Blocked — 6 load-bearing parameters without primary lit (STRC mRNA t½, STRC protein t½, STRC copy
7indexC321Wet-lab ribosome-profiling STRCP1
8indexC232Phase 3a morpholino + 3b gapmer
15indexD222Chimera dead; upregulation weak
16indexD321Wrong patient (paternal 98kb Δ)
3indexS554Order Ultra-Mini gBlock + B8+WPRE3 cassette; clone pAAV B8-IgK-Ultra-Mini-WPRE3-bGH; Phase 4 HEK coIP. Verify B8 exact cloned sequence against Zhao 2025 Table S2 before GMP submission (cloning QC, not design blocker).
9indexS543Reviewer-pack queue staged 2026-04-27 after Phase 4m S promotion. Next sessions should start at STRC h09 Reviewer Pack Queue 2026-04-27 and work in order: premortem → precedent table → orthogonal WH2 controls → transfer memo. Phase 4m remains the gate-closing evidence (R2=0.690, Kd_F=1.48 mM); Phase 4k is a supporting caution (geometric contacts yes, confidence-supported contacts no). Phase 4l optional only if a reviewer needs paper-grade C_eff.

Papers (most recent)

TABLE WITHOUT ID
  file.link AS "Paper",
  year AS "Year",
  kind AS "Kind",
  read AS "Read",
  read_for AS "For"
FROM "sources/lit"
WHERE type = "lit"
SORT year DESC, file.mtime DESC
LIMIT 20
PaperYearKindReadFor
Omichi_2020_AAV_hair_cell_transductionpaper
Gadenstaetter_2024_inner_ear_gene_therapy_reviewreview
Verpy_2008_Stereocilin_Naturepaper
verpy-2011-strc-tm-morphologypaper
tarchini-2021-strc-dual-vector-neonatalpaper
dulon-2019-htc-bundle-mechanicspaper
Stiffness and tension gradients of the hair cell’s tip-link complex in the mammalian cochleabook
Zhu 2019 - Single-cell proteomics reveals changes in expression during hair-cellbook
Rivera 2019 - Cochlear outer hair cell horizontal top connectors mediate maturebook
Mendell_2020_micro_dystrophin_clinicalpaper
Deep Research - STRC Hearing Loss Treatmentreport
Cochlear outer hair cell horizontal top connectors mediate mature stereocilia bundle mechanicsbook
2026-sang-af3-turboab-antibody-structural-prediction2026paperTrueh03, h09, h26
2026-harvey-afm-nanobody-gpcr2026paperTrueh09, h26
2026-01-iranfar-dual-aav-strc-ctm2026paper
2026-sun-rbm24-alternative-splicing-cochlear2026paper
2026-04-22-jiang-multicentre-gene-therapy-for2026paper
2026-04-21-zhilkin-cvfest-mutation-kinetics2026paper
2026-04-21-yin-piezoelectric-pvdf-bt-bone2026paper
2026-04-21-wu-pvdf-trfe-pedotpss-piezoelectric2026paper

Core concept notes

LIST file.link
FROM "notes"
WHERE contains(tags, "strc") AND type = "note"
SORT file.name ASC

Literature topics

LIST file.link
FROM "parameters"
WHERE type = "literature-topic"
SORT file.name ASC

(no results)

External stubs (Brain-vault bridges)

LIST file.link
FROM "external"
WHERE type = "external-stub"
SORT file.name ASC

Connections

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