CRISPR/Cas9-Based Therapy for Patients With Autosomal Dominant Retinitis Pigmentosa

Tech ID: wan000892



Retinitis pigmentosa (RP) is an inherited retinal disease that causes progressive photoreceptor degeneration and continual vision loss, often resulting in complete blindness by middle age. RP is one of the most common inherited diseases of the retina, affecting 1 in 4,000 people in the U.S. and Europe, i.e. 1.5 million patients worldwide. Mutations in more than 60 genes are known to cause nonsyndromic RP, with approximately 40% of mutations classified as autosomal dominant. Mutations in the rhodopsin (RHO) gene are the most common cause of autosomal dominant RP, accounting for 20 to 30 percent of all cases.


Technology Description 

Inventors showed that CRISPR/Cas9 can be used in vivo to selectively inactivate the rhodopsin gene carrying the dominant S334ter mutation (RhoS334) in rats that model severe autosomal dominant RP. A single subretinal injection of guide RNA (gRNA)/Cas9 plasmid in combination with electroporation generated allele-specific disruption of RhoS334, which prevented retinal degeneration and improved visual function.



Gene replacement therapy is being evaluated for the recessive form of RP, in which both inherited alleles are dysfunctional. However, RP arising from dominant mutations would not benefit from this approach because mutant RhoS334 production is unaffected.  The inventors were the first to demonstrate that targeted [functional] ablation of an RP-causing gene in live animals can prevent retinal dystrophy and vision loss.  No alternative therapeutic approaches have demonstrated equivalent efficacy. The technology under development will use viral delivery of a CRISPR/Cas9-based therapy to selectively inactivate an RP-causing mutant allele, while not affecting the wild-type Rho Allele. A novel safety design feature under investigation is planned for incorporation into the proposed therapeutic to ensure safety from off-target events.



The technology may be developed into a novel gene-editing therapy to treat autosomal dominant RP in patients.


Intellectual Property 

US utility patent application 15/130,846 filed.



• Bakondi et al. In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Dominant Retinitis Pigmentosa. Molecular Therapy. 2016, 24(3):556-63 [Link]


Patent Information:
For Information, Contact:
Wenyue Du
Senior Associate - IP Management & Licensing
Shaomei Wang
Wenjian Lv
Benjamin Bakondi
Bin Lu
Gene Therapy