Combination Vector May Rescue Vision by Functionally Substituting Harmful Forms of the Rhodopsin Gene with Normal, Healthy Copies
This combination adeno-associated virus (AAV) vector may delay progression of autosomal dominant retinitis pigmentosa associated with rhodopsin mutations by enabling degradation of harmful forms of the rhodopsin gene and replacement with normal, healthy copies. Autosomal dominant retinitis pigmentosa, a form of retinal degeneration, is an eye disease that causes progressive vision loss in 1 in 20,000 individuals worldwide. This disease is frequently caused by a variety of mutations in the gene that controls rhodopsin, a pigment that is vital to the function of photoreceptor cells within the retina. Autosomal dominant retinitis pigmentosa causes progressive loss of peripheral vision and onset of tunnel vision, and eventually results in legal blindness in nearly all affected patients. Treatment is largely limited to vitamin A supplements and retinal prosthesis devices- there are no available pharmaceutical or gene therapy approaches to treat autosomal dominant retinitis pigmentosa. Researchers at the University of Florida have developed a combination AAV vector that may delay progression of autosomal dominant retinitis pigmentosa by suppressing destructive forms of rhodopsin and introducing normal, healthy rhodopsin into diseased photoreceptor cells. This combination vector therapy may improve eyesight soon after injection and enable continuous repair of cells already damaged by harmful rhodopsin mutations, enhancing recovery prospects for patients with autosomal dominant retinitis pigmentosa..
Combination AAV vector silences defective forms of the rhodopsin gene, replacing them with healthy copies, to delay progression of autosomal dominant retinitis pigmentosa
- Removes damaged forms of rhodopsin, potentially slowing destruction of photoreceptors and resulting retinal degeneration
- Uses AAV vectors that function in humans and in some animals, providing a possible low-vision therapy for the veterinary disease market
- Combination vector contains silencing RNA and healthy rhodopsin gene, avoiding safety complications associated with multiple treatments or increased injection volumes
This combination AAV vector utilizes an RNA interference strategy to silence expression of often-toxic, endogenous rhodopsin in photoreceptors affected by autosomal dominant retinitis pigmentosa, while introducing normal, healthy copies of the rhodopsin gene to treated photoreceptor cells. Importantly, the replacement copies of rhodopsin are unaffected by the RNA interference strategy. This strategy may enable repair of accumulated photoreceptor damage caused by toxic rhodopsin mutations, while quickly enhancing visual function with new, healthy rhodopsin. Additionally, combination therapy avoids risks associated with multiple ocular therapeutic injections, as well as losses in efficacy associated with a dual-vector co-infection strategy. This AAV vector may dramatically alter the treatment landscape for patients with autosomal dominant retinitis pigmentosa.