Gene Therapy and Eye Disease

Palo Alto, CA — Dr. Vinit Mahajan and Dr. Stephen Tsang of Columbia University, along with their trainees, have written several review articles about gene therapy and eye disease in an effort to keep researchers abreast of cutting-edge technologies that are transforming treatment plans and patient care. 

“With over 20 gene therapy clinical trials in the pipeline, it is important to stay informed of all of the changes that are happening with gene therapy,” Tsang said.

With a focus on precision health, researchers have made enormous strides in genome sequencing and analysis, gene delivery, and genome surgery as they narrow in on the molecular causes of disease.

“Our review articles give an overview that we think physicians and scientists can use as they plan for the changing landscape of precision medicine in ophthalmology,” explained Dr. Mahajan. 

The anatomy of the eye with its compartmentalization and unique anatomy that is accessible to surgeons at the cellular level make it the perfect organ for gene therapy. This has been demonstrated in numerous ongoing ophthalmology clinical trials. 

The structure of the eye makes it ideal for gene therapy, but so does its unique relationship with the immune system that helps dampen inflammatory responses, and its duplicity as an organ allows for one eye to be tested and the other to serve as a control. Breakthroughs in viral and non-viral gene vectors have allowed for the delivery of genetic payloads in preclinical models of retinal disorders. 

Mahajan was a surgeon on the phase-3 LCA human gene therapy trial, which is now approved by the FDA. This landmark trial opens the window for targeting other retinal disease genes.

There is ongoing  progress using gene therapy and genome editing for several retinal genetic disorders, including RPE65, CEP290, and GUY2D-associated Leber congenital amaurosis, as well as choroideremia, achromatopsia, Mer tyrosine kinase– (MERTK–) and RPGR X-linked retinitis pigmentosa, Usher syndrome, neovascular age-related macular degeneration, X-linked retinoschisis, Stargardt disease, and Leber hereditary optic neuropathy. The recent Mahajan-Tsang papers review these topics.

crispr-cas_genome_surgery_in_opththalmology.pdf

gene_therapy_and_genome.pdf

genome_surgery_and_gene_therapy_in_retinal_disorders.pdf

translation_of_crispr_genome_surgery_to_the_bedside_for_retinal_diseases.pdf