Gene Therapy for Treatment of CRX-Autosomal Dominant Retinopathies

Mutations in the cone rod homeobox (CRX) transcription factor lead to distinct retinopathy phenotypes, including early-onset vision impairment in dominant Leber congenital amaurosis (LCA). Adeno-Associated virus (AAV) vector-mediated delivery of a CRX cDNA under the control of a CRX promoter region partially restored photoreceptor phenotype and expression of phototransduction genes in an in vitro model of CRX-LCA. Gene therapy using the CRX-AAV vector to retinal organoids derived from induced pluripotent stem cells (iPSCs) of a patient with the dominant CRX-I138fs mutation partially restored expression of visual opsins and other phototransduction genes as revealed by immunohistochemistry and single cell RNA-sequencing. Retinal organoids from iPSCs of a second dominant CRX-LCA patient carrying a K88N mutation also revealed loss of expression of opsins and phototransduction genes as a common phenotype, which could be alleviated by AAV-mediated overexpression of CRX. 

Potential Commercial Applications: Competitive Advantages:
  • Early onset blindness, including Leber congenital amaurosis
  • Gene therapy of CRX retinopathies; i.e., patients with a mutation in the CRX gene
  • Promising commercial potential given that there are no current treatments for CRX-retinopathies 
  • Gene therapy by delivering CRX should restore photoreceptor structure and function
  • Existing commercial interest and an established regulatory path for directly administered gene therapy targeting an ophthalmic disease caused by mutations in a specific gene: In 2017, Luxturna (voretigene neparvovec-rzyl) was FDA approved for an inherited form of vision loss (confirmed biallelic RPE65 mutation-associated retinal dystrophy) that may result in blindness

Development Stage:
Discovery (Lead Identification)


Anand Swaroop (NEI)  ➽ more inventions...

Kamil Kruczek (NEI)  ➽ more inventions...

Zhijian Wu (NEI)  ➽ more inventions...

Suja Hiriyanna (NEI)  ➽ more inventions...

Intellectual Property:
Application No. 62/962,732

Collaboration Opportunity:

Licensing and research collaboration

Licensing Contact:
John Hewes, Ph.D.
Phone: 240-276-5515

OTT Reference No: E-008-2020
Updated: Aug 17, 2020