Human rhodopsin (RHO) promoter
Proximal promoter region of the human rhodopsin (RHO) gene, restricting expression to rod photoreceptors of the retina. Used in AAV vectors combining RHO-targeted knockdown with mutation-independent RHO replacement for gene therapy of rhodopsin-linked autosomal dominant retinitis pigmentosa.
Origin: Human rhodopsin (RHO) gene, proximal promoter fragment
Characteristics
The RHO gene itself contains four introns and encodes a 348-residue protein 93.4% identical to bovine rhodopsin; its proximal promoter region drives expression restricted to rod photoreceptors. A single AAV2/5 vector combining shRNA-mediated knockdown of endogenous (mutant) RHO under an H1 promoter with an shRNA-resistant replacement RHO coding sequence under a 536 bp region of this proximal promoter achieves mutation-independent rescue in a canine model of autosomal dominant retinitis pigmentosa, halting photoreceptor degeneration regardless of the specific RHO mutation present.
Applications: Rod-restricted transgene expression in AAV vectors for gene therapy of rhodopsin-linked autosomal dominant retinitis pigmentosa, including combined knockdown-and-replacement constructs that do not depend on the specific causative RHO mutation.
Limitations: AAV packaging capacity constrains promoter size, so only the proximal several-hundred-bp region is used rather than the full regulatory locus; unlike the human rhodopsin kinase (hGRK1) promoter, this proximal RHO promoter targets rods only and does not co-target cones.