Shahin Saba, Xu Hui, Lu Bin, Mercado Augustus, Jones Melissa K, Bakondi Benjamin, Wang Shaomei
Board of Governors Regenerative Medicine Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Pharmaceutics. 2022 Apr 9;14(4):824. doi: 10.3390/pharmaceutics14040824.
Retinitis pigmentosa (RP) consists of a group of inherited, retinal degenerative disorders and is characterized by progressive loss of rod photoreceptors and eventual degeneration of cones in advanced stages, resulting in vision loss or blindness. Gene therapy has been effective in treating autosomal recessive RP (arRP). However, limited options are available for patients with autosomal dominant RP (adRP). In vivo gene editing may be a therapeutic option to treat adRP. We previously rescued vision in neonatal adRP rats by the selective ablation of the Rhodopsin S334ter transgene following electroporation of a CRISPR/Cas9 vector. However, the translational feasibility and long-term safety and efficacy of ablation therapy is unclear. To this end, we show that AAV delivery of a CRISPR/Cas9 construct disrupted the Rhodopsin P23H transgene in postnatal rats, which rescued long-term vision and retinal morphology.
视网膜色素变性（RP）是一组遗传性视网膜退行性疾病，其特征是视杆光感受器逐渐丧失，在晚期锥体细胞最终退化，导致视力丧失或失明。基因治疗已有效地治疗常染色体隐性视网膜色素变性（arRP）。然而，对于常染色体显性视网膜色素变性（adRP）患者，可用的治疗选择有限。体内基因编辑可能是治疗adRP的一种治疗选择。我们之前通过在电穿孔CRISPR/Cas9载体后选择性切除视紫红质S334ter转基因，拯救了新生adRP大鼠的视力。然而，切除疗法的转化可行性以及长期安全性和有效性尚不清楚。为此，我们表明，通过腺相关病毒（AAV）递送CRISPR/Cas9构建体，可破坏出生后大鼠的视紫红质P23H转基因，从而挽救长期视力和视网膜形态。
