AAV-ZF-RHO

AAV-ZF-RHO is an adeno-associated virus (AAV)-based gene therapy candidate designed for the treatment of Rhodopsin Autosomal Dominant Retinitis Pigmentosa (RHO-ADRP). Developed by researchers at the University of Naples Federico II, the University of Bologna, and Universitat Klinikum Freiburg, the therapy employs a mutation-agnostic "silence and replace" strategy. It utilizes a single AAV vector containing two independent expression cassettes: one encoding a Zinc Finger DNA-binding protein (ZF-RHO) that represses endogenous rhodopsin (RHO) expression, and another providing a wild-type RHO replacement gene. The system is governed by a synthetic circuit where the ZF-RHO protein binds to the endogenous RHO promoter, its own promoter (feedback), and the replacement gene's promoter (feedforward) to achieve precise transcriptional control and improved safety.