This technology is a collection of optimized therapeutic prime-editing strategies targeting a hotspot of splicing mutations in the peripherin‐2 gene (PRPH2) that are associated with multiple retinal degenerations.
Unmet Need: No targeted therapeutics against peripherin‐2 gene (PRPH2) that mediates retinal degeneration
There are no therapeutics on the market to treat peripherin‐2 (PRPH2) mutations, which are associated with a variety of retinal degenerations including macular dystrophy and cone‐rod dystrophy.
The Technology: Gene augmentation methods and systems for PRPH2 retinal dystrophy therapeutics
This technology encompasses a series of methods and systems to correct the +1,+2 and +3 c.828 splice site PRPH2 mutations. The method uses prime-editing to modify c.828+ mutations in PRPH2 by a modified version of the Cas9 nickase-reverse transcriptase, optimized pegRNA, and nicking sgRNA to generate systems to be configured for delivery to retinal cells.
This technology was validated during in vivo experiments using patient induced pluripotent stem cell (iPSC)-derived retinal organoids.
Applications:
- Method for modifying a gene using prime-editing
- Prime-editing therapeutic strategy consisting of a variety of the following: Cas protein, a reverse transcriptase, RNA spacer or extension sequence, and a nicking guide RNA (ngRNA)
- Package to correct the +1, +2 and +3 c.828 PRPH2 patient mutations, which includes the second most reported variant
- Treatment for retinal degeneration, retinitis pigmentosa, macular degeneration, macular dystrophy, fundus flavimaculatus-like dystrophy, central areolar choroidal dystrophy, and cone-rod dystrophy
- Methods can be developed to similarly edit optical dystrophies domestic animal and livestock breeding industries
Advantages:
- Can correct several splice mutations with a single therapeutic design
- Can be easily converted into a genome therapeutic product using AAV or lentiviruses
- Enables precise base edits of patient-derived mutations
- Research tool capable of studying complex base transitions and conversions
- Can be developed into a clinical treatment or preventive for patients with PRPH2 mutations
Lead Inventor:
Stephen H. Tsang, M.D., Ph.D.
Patent Information:
Patent Pending (WO/2023/220732)
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