Single AAV-mediated mutation replacement genome editing in limited number of photoreceptors restores vision in mice

Koji M. Nishiguchi, Kosuke Fujita, Fuyuki Miya, Shota Katayama, Toru Nakazawa

研究成果: Article査読

18 被引用数 (Scopus)

抄録

Supplementing wildtype copies of functionally defective genes with adeno-associated virus (AAV) is a strategy being explored clinically for various retinal dystrophies. However, the low cargo limit of this vector allows its use in only a fraction of patients with mutations in relatively small pathogenic genes. To overcome this issue, we developed a single AAV platform that allows local replacement of a mutated sequence with its wildtype counterpart, based on combined CRISPR-Cas9 and micro-homology-mediated end-joining (MMEJ). In blind mice, the mutation replacement rescued approximately 10% of photoreceptors, resulting in an improvement in light sensitivity and an increase in visual acuity. These effects were comparable to restoration mediated by gene supplementation, which targets a greater number of photoreceptors. This strategy may be applied for the treatment of inherited disorders caused by mutations in larger genes, for which conventional gene supplementation therapy is not currently feasible.

本文言語English
論文番号482
ジャーナルNature communications
11
1
DOI
出版ステータスPublished - 2020 12月 1
外部発表はい

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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