Technologies
This technology is an allele-specific prime editing approach designed to enable precise, mutation-targeted modification of the rhodopsin (RHO) gene associated with inherited retinal disorders.
Inherited retinal disorders (IRDs), including retinitis pigmentosa, are genetically heterogeneous neurodegenerative diseases that lead to progressive vision loss and blindness. Currently, there is only one FDA-approved gene therapy, which targets a single mutation, leaving most patients without effective therapeutic options. The existing gene editing strategies often rely on double-stranded DNA breaks, which can introduce off-target effects, genomic instability, and safety concerns, particularly in post-mitotic tissues such as the retina. There is a need for precise, mutation-specific therapeutic approaches that safely address dominant pathogenic alleles while preserving normal gene function.
This technology utilizes a prime editing platform to selectively target pathogenic mutations in the rhodopsin (RHO) gene, which is associated with autosomal dominant retinitis pigmentosa. This approach utilizes a Cas H840 nickase fused to reverse transcriptase, guided by engineered prime editing guide RNAs (pegRNAs), to introduce precise nucleotide modifications without creating double-stranded DNA breaks. This technology selectively silences the mutant RHO allele while preserving expression of the wild-type allele, thus maintaining retinal function. This allele-specific strategy reduces off-target effects and avoids genomic instability.
The technology has been validated in vitro using human 293T cells, showing high specificity and approximately 50% editing efficiency.
Patent Pending (WO/2025/259694)