Synthetic fusion promoters improve balanced transgene expression in rods and cones in retinal gene therapy preprint

Achieving efficient transgene expression across both rod and cone photoreceptors is a persistent challenge in retinal gene therapy research. Current promoter constructs tend either to lack cell-type specificity or to provide insufficient coverage of both photoreceptor types at adequate expression levels. A preprint posted to bioRxiv in June 2026 describes two synthetic fusion promoters, designated Pikali and Nocchu, generated by combining PR1.7 (a cone-specific promoter) with GRK1 (a promoter most active in rods).

The authors report that both fusion promoters outperformed their parental constructs in driving GFP expression across rods and cones in human iPSC-derived retinal organoids. If confirmed after peer review, the findings could inform the design of future photoreceptor-targeted gene therapy vectors for inherited retinal dystrophies, a group of conditions caused by single-gene defects affecting the retina.

The work is of primary interest to researchers in retinal gene therapy, ocular genetics, and vector biology. Educators and students studying gene therapy delivery mechanisms may also find the promoter engineering approach instructive. The preprint has not yet been peer-reviewed.