In vivo prime editing rescues photoreceptor degeneration in nonsense mutant retinitis pigmentosa

Yidian Fu, Xiaoyu He, Liang Ma, Xin D. Gao, Pengpeng Liu, Hanhan Shi, Peiwei Chai, Shengfang Ge, Renbing Jia, David R. Liu, Xianqun Fan () and Zhi Yang ()
Additional contact information
Yidian Fu: Shanghai Jiao Tong University School of Medicine
Xiaoyu He: Shanghai Jiao Tong University School of Medicine
Liang Ma: Shanghai Jiao Tong University School of Medicine
Xin D. Gao: Broad Institute of Harvard and MIT
Pengpeng Liu: Southern University of Science and Technology
Hanhan Shi: Shanghai Jiao Tong University School of Medicine
Peiwei Chai: Shanghai Jiao Tong University School of Medicine
Shengfang Ge: Shanghai Jiao Tong University School of Medicine
Renbing Jia: Shanghai Jiao Tong University School of Medicine
David R. Liu: Broad Institute of Harvard and MIT
Xianqun Fan: Shanghai Jiao Tong University School of Medicine
Zhi Yang: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract The next-generation gene editing tool, prime editing (PE), is adept at correcting point mutations precisely with high editing efficiency and rare off-target events and shows promising therapeutic value in treating hereditary diseases. Retinitis pigmentosa (RP) is the most common type of inherited retinal dystrophy and is characterized by progressive degeneration of retinal photoreceptors and, consequently, visual decline. To date, effective treatments for RP are lacking. Herein, a PE system is designed to target the PDE6B Y347X mutation in the rd1 mouse strain, a preclinical RP model. We screen and develop the PE system with epegRNA and RTΔRnH, which is delivered via dual-AAV in vivo with an editing efficiency of 26.47 ± 13.35%, with negligible off-target effects confirmed by AID-Seq and PE-tag. Treatment with the PE system in vivo greatly restores PDE6B protein expression and protects rod cells from degeneration. Mouse behavioural experiments also show that compared with no treatment, prime editing inhibits vision deterioration in littermate rd1 mice. This study provides a therapeutic opportunity for the use of PE to correct mutated RPs at the genomic level.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57628-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57628-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57628-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().