Computational hypotheses for accelerating STRC gene therapy. These require experimental validation.
Three single-AAV constructs validated by 16 AF3 experiments. Removing the disordered N-terminal improves folding (pTM 0.81-0.87). Recommended: shorter mini-STRC (3228 bp, 1472 bp headroom).
Precision correction of c.4976A>C using PE3 or PE3b pegRNA strategy without double-strand breaks.
Mechanosensitive channel activation via focused ultrasound. ODE model of calcium signaling in OHC stereocilia.
Non-invasive cochlear gene delivery via sonoporation + LNP. ODE model shows 78% transduction efficiency under optimized parameters.
Poisson stochastic model quantifying the probability cost of dual-vector co-transduction vs single-vector strategy.
Coulomb energetics explain why E1659A is pathogenic despite intact structure. 8.62 kcal/mol destabilization of adhesion interface.
NAb kinetics, seroprevalence barriers, and delivery vehicle comparison for cochlear gene therapy re-dosing strategies.
ARBITER workflow for OHC-specific synthetic enhancers. B8 enhancer fully rescues hearing with zero ectopic expression. Potential synergy with mini-STRC for single-vector therapy.
Antisense oligonucleotides to skip mutant exons, producing shorter but functional stereocilin. Repeatable, no AAV needed. Proven in DMD (4 FDA-approved drugs).