Preprint reports mutation-agnostic gene insertion strategy for rhodopsin-linked retinitis pigmentosa

Researchers have posted a preprint to bioRxiv describing a mutation-agnostic gene insertion strategy for autosomal dominant retinitis pigmentosa caused by mutations in the rhodopsin gene (RHO-adRP). RHO-adRP is among the more common inherited retinal dystrophies; nearly 100 distinct pathogenic variants have been identified in the RHO gene, making it impractical to develop a separate therapeutic for each mutation. The strategy presented uses zinc finger nucleases — sequence-specific DNA-cutting proteins — to achieve homology-independent targeted integration (HITI) of a functional gene copy at the RHO 5' untranslated region.

By targeting a fixed genomic site rather than correcting individual mutations, the approach is in principle applicable to patients carrying any of the known RHO pathogenic variants. The preprint reports preclinical efficacy and safety data including proof-of-concept experiments, though the authors note the work remains at an early translational stage.

Inherited retinal dystrophies have been a focus of gene therapy research for over a decade; the first approved gene therapy for an inherited retinal condition (targeting RPE65) received regulatory clearance in the United States in 2017. The zinc finger nuclease platform used here is distinct from CRISPR-based approaches and has its own established safety and delivery profile. This work is a preprint and has not yet completed peer review.