与其替换整个STRC基因（5325 bp），能否只纠正那一个突变碱基？基因编辑工具共有三种类型。我针对Michael的具体变异逐一进行了检验。
先导编辑需要靶点附近存在"着陆点"（PAM位点，NGG序列）。我从Ensembl REST API下载了变异周围的基因组序列，并搜索了变异位点15 bp范围内的NGG基序。
Precise gene editing has been demonstrated in cochlear OHCs with functional hearing recovery:
Zhang et al. 2025 (Nature Communications): ABE (SchABE8e) delivered via Anc80L65 AAV to neonatal mice. Targeted a stop codon in POU4F3 (hair cell transcription factor). Near-complete hearing recovery sustained 4+ months. This is the most relevant proof: same AAV serotype used for STRC gene therapy, same cells, functional rescue.
Chen et al. 2024 (Nature Biotechnology): Dual-AAV split-intein prime editor in adult mouse brain. Up to 42% editing in post-mitotic cortical neurons. Also 35% in iPSC-derived cardiomyocytes (Chemla 2025). OHCs are similarly post-mitotic — these are the best efficiency benchmarks available.
No one has prime-edited a cochlear OHC yet. But the full chain is proven in pieces: AAV reaches OHCs (Fang 2021, Iranfar 2026), ABE in OHCs restores hearing (Zhang 2025), and dual-AAV PE achieves ~42% in post-mitotic neurons (Chen 2024). The specific edit for Misha requires PE or ACBE — both are the remaining gaps to close.
现实评估：先导编辑尚未在体内内耳毛细胞中进行测试。将先导编辑器与引导RNA递送至耳蜗深部外毛细胞，仍是一项尚未解决的挑战。但本分析证实，Michael的具体变异在技术上是可靶向的。若递送问题得以解决（目前是活跃的研究领域），该突变即可在DNA层面得到纠正。