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: |
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Development Stage:
Discovery (Lead Identification)
Inventors:
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.
Email: John.Hewes@nih.gov
Phone: 240-276-5515
OTT Reference No: E-008-2020
Updated: Aug 17, 2020