STRC Gene Therapy

TL;DR: STRC coding (~6 kb) exceeds AAV packaging (~4.7 kb), blocking single-vector delivery. Shu Yilai lab (Fudan EENT) is actively developing STRC therapy; Egor’s mini-STRC truncated-protein concept was forwarded to Dr. Han Shuang. Jeffrey Holt lab (Harvard/BCH) also in the loop.

Gene therapy for STRC-related hearing loss (DFNB16). STRC encodes stereocilin (~6 kb coding), which exceeds the AAV packaging limit (~4.7 kb), making single-vector delivery a challenge.

Active Research

• Shu Yilai Lab (Fudan EENT) — actively developing STRC gene therapy drugs as of April 2026. Dr. Han Shuang (韩双) leads the animal research arm.
• Jeffrey Holt Lab (Harvard/BCH) — Egor is in contact regarding STRC + mini-STRC + TMEM145 research

mini-STRC Single-Vector Approach

Egor proposed a mini-STRC single-vector gene therapy concept to the Shu team. This approach would use a truncated but functional version of stereocilin that fits within AAV packaging limits. The idea was forwarded to Dr. Han Shuang for consideration in their animal model work.

Challenges

• STRC coding sequence is ~6 kb — too large for standard AAV single-vector
• Dual-vector strategies exist but have lower efficiency
• mini-gene approach (analogous to mini-dystrophin) could be a solution
• Pseudo-STRC gene complicates genetic diagnosis

Research Notes

• Adult Treatment Window STRC — [source] evidence for adult treatment viability
• Base Editing Cochlear Precedent 2024 — [source] base editing precedent in cochlea
• Cochlear AAV Inflammation 2025 — [source] AAV inflammation risks in cochlea
• Extracellular Vesicle Delivery Cochlea 2024 — [source] alternative non-viral delivery method
• RNA Editing Hearing Loss Rznomics — [source] RNA editing approach to hearing loss
• STRC AC1-CREB Alternative Hypothesis — [extends] alternative therapeutic hypothesis
• STRC Long-Read Diagnostics 2025 — [source] long-read sequencing for STRC diagnostics
• Alternative STRC Delivery Hypotheses — [extends] non-AAV delivery options
• Activity-Dependent Closed-Loop Therapy — [extends] closed-loop therapy concept
• STRC Stereocilia Bundle Mechanics Model — [extends] biophysical model predicting ~35 dB ABR improvement at 67% transduction
• STRC Research Monitor Pipeline — nightly Claude agent scanning PubMed, scoring papers against the STRC Hypothesis Ranking, publishing to strc.egor.lol
• AlphaGenome — [applies] Google DeepMind foundation model for variant effect prediction; relevant for STRC c.4976A>C regulatory/splicing analysis

Connections

• STRC Variant c.4976A>C — Misha — [applies] potential treatment for Misha’s condition
• Shu Yilai Lab — Fudan EENT — [source] lead research group
• 2026-04-07-chen-liheng-strc-reply — [source] confirmed active development
• [part-of] MOC - Psychology & ADHD