Allele-specific prime editing strategies for rhodopsin-mediated retinitis pigmentosa
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.
Unmet Need: Safe, mutation-specific therapies for inherited retinal degeneration
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.
The Technology: Allele-specific prime editing for rhodopsin-associated retinal disorders
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.
Applications:
- Allele-specific prime gene editing therapy for inherited retinal diseases, including autosomal dominant retinitis pigmentosa (RHO-associated) and other domain retinal degenerations caused by toxic gain-of-function alleles
- In vivo model for photoreceptor degeneration
- Research tool for heterozygous gene silencing
Advantages:
- Allele-specific targeting preserves wild-type gene function
- Avoids double-stranded DNA breaks, reducing genomic instability
- High specificity with reduced off-target editing
- Scalable and adaptable to multiple RHO mutations
- Compatible with post-mitotic retinal tissue
- Potential for broad applicability across inherited retinal disorders
Lead Inventor:
Patent Information:
Patent Pending (WO/2025/259694)
Related Publications:
Tech Ventures Reference:
- Licensing Contact: Kristin Neuman