Chop-Stick gene therapy for retinitis pigmentosa and other autosomal dominant ocular diseases

This technology uses CRISPR-Cas gene editing to disrupt and correct ocular disease-associated mutated genes, resulting in improved protein function and disease treatment.

Unmet Need: Effective treatment for autosomal dominant ocular diseases

Retinal degenerative diseases affect quality of life for millions of people around the world. Amongst the most severe is retinitis pigmentosa (RP), which results in progressive vision loss due to a loss of rod photoreceptor cells, followed by cone degeneration. The autosomal dominant forms of RP can be caused by a number of genetic mutations, but are most commonly caused by hereditary mutations in the rhodopsin (RHO) gene. While some treatments have been developed to alleviate symptoms, there is currently no cure for RP. Existing gene therapies that simply supply additional healthy genes to a patient are not sufficient, as the mutated gene still remains present.

The Technology: Mutation-independent gene therapy for treating multiple autosomal dominant ocular diseases

This technology modifies an autosomal dominant disease-associated gene, such as rhodopsin (RHO), through a two-step “Chop-Stick” process. First, an adeno-associated viral vector encoding a CRISPR-Cas system is used to partially or completely disrupt (“Chop”) both mutant and wild type alleles of the RHO gene from the RP patient, then introduce (“Stick”) a codon-modified cDNA sequence containing the wild type allele to restore, correct, supplement, or augment protein function. This system is not mutation-specific, allowing for gene editing of any mutation on that gene. This technology could also be modified to target other genes for the treatment of other autosomal dominant diseases.

This technology has been used to preserve the photoreceptors in a mouse model. It has also been used to edit the RHO gene in human induced pluripotent stem cells (iPSCs).

Applications:

• Treatment for all variants of rhodopsin-dependent retinitis pigmentosa (RP)
• Treatment of retinopathy, Doyne honeycomb retinal dystrophy, and/or macular degeneration
• Treatment for other diseases cause by autosomal dominant genetic mutations

Advantages:

• Gene editing is not mutation-specific allowing for treatment of multiple genetic variants
• Less invasive and fewer complications than retinal implant therapy

Lead Inventor:

Stephen H. Tsang M.D., Ph.D.

Patent Information:

Patent Status

Related Publications:

• Wert KJ, Davis RJ, Sancho-Pelluz J, Nishina PM, Tsang SH. “Gene therapy provides long-term visual function in a pre-clinical model of retinitis pigmentosa.” Hum Mol Genet. 2013 Feb 1;22(3):558-67.

• Li Y, Chan L, Nguyen HV, Tsang SH. “Personalized Medicine: Cell and Gene Therapy Based on Patient-Specific iPSC-Derived Retinal Pigment Epithelium Cells.” Adv Exp Med Biol. 2016; 854:549-55.

• Bassuk AG, Zheng A, Li Y, Tsang SH, Mahajan VB. “Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells.” Sci Rep. 2016 Jan 27;6: 19969.

Tech Ventures Reference:

• IR CU15206, CU18283

• Licensing Contact: Kristin Neuman