A phase 1–2 clinical trial evaluated the safety and efficacy of EDIT-101, a CRISPR-Cas9 gene-editing therapy, for CEP290-associated inherited retinal degeneration. The study enrolled 14 participants (12 adults and 2 children) with a pathogenic variant in intron 26 of the CEP290 gene. EDIT-101 was administered via subretinal injection in the worse-seeing eye. The primary outcome was safety, with no serious adverse events or dose-limiting toxicities reported. Key secondary outcomes included improvements in visual acuity, retinal sensitivity, mobility, and quality of life. Six participants showed meaningful improvement in cone-mediated vision, with five also showing improvement in other outcomes. Nine participants had meaningful improvements in visual acuity, retinal sensitivity, or mobility. Six participants showed meaningful improvements in quality of life. The study demonstrated that EDIT-101 was well-tolerated and led to improvements in photoreceptor function, supporting further research into CRISPR-Cas9 gene editing for inherited retinal degenerations. CEP290-associated retinal degeneration is a severe condition causing early-onset vision loss due to mutations in the CEP290 gene. The most common variant, IVS26, leads to the inclusion of a cryptic exon, disrupting CEP290 expression. No approved treatments exist, and supportive interventions are the standard of care. Experimental approaches include antisense oligonucleotides and gene delivery, but these have limited efficacy. EDIT-101 targets the IVS26 variant, using an AAV5 vector with SaCas9 and specific guide RNAs. The study showed that EDIT-101 improved retinal sensitivity, visual acuity, and mobility in participants. The results suggest that in vivo CRISPR-Cas9 gene editing could be a promising treatment for CEP290-associated retinal degeneration and other genetic causes. The study highlights the potential of gene editing to restore vision in patients with inherited retinal degenerations.A phase 1–2 clinical trial evaluated the safety and efficacy of EDIT-101, a CRISPR-Cas9 gene-editing therapy, for CEP290-associated inherited retinal degeneration. The study enrolled 14 participants (12 adults and 2 children) with a pathogenic variant in intron 26 of the CEP290 gene. EDIT-101 was administered via subretinal injection in the worse-seeing eye. The primary outcome was safety, with no serious adverse events or dose-limiting toxicities reported. Key secondary outcomes included improvements in visual acuity, retinal sensitivity, mobility, and quality of life. Six participants showed meaningful improvement in cone-mediated vision, with five also showing improvement in other outcomes. Nine participants had meaningful improvements in visual acuity, retinal sensitivity, or mobility. Six participants showed meaningful improvements in quality of life. The study demonstrated that EDIT-101 was well-tolerated and led to improvements in photoreceptor function, supporting further research into CRISPR-Cas9 gene editing for inherited retinal degenerations. CEP290-associated retinal degeneration is a severe condition causing early-onset vision loss due to mutations in the CEP290 gene. The most common variant, IVS26, leads to the inclusion of a cryptic exon, disrupting CEP290 expression. No approved treatments exist, and supportive interventions are the standard of care. Experimental approaches include antisense oligonucleotides and gene delivery, but these have limited efficacy. EDIT-101 targets the IVS26 variant, using an AAV5 vector with SaCas9 and specific guide RNAs. The study showed that EDIT-101 improved retinal sensitivity, visual acuity, and mobility in participants. The results suggest that in vivo CRISPR-Cas9 gene editing could be a promising treatment for CEP290-associated retinal degeneration and other genetic causes. The study highlights the potential of gene editing to restore vision in patients with inherited retinal degenerations.