Editas Developing Gene-Editing Therapy for Leber Congenital Amaurosis (CEP290 Mutations)

August 13, 2015

While announcing $120 million in new venture-capital funding, the emerging gene-editing company Editas also reports that it’s developing a treatment for the retinal disease Leber congenital amaurosis (LCA) caused by mutations in the gene CEP290. 

The company hasn’t provided a timetable for moving its CEP290 gene-editing therapy into human trials. However, Editas reports that, back in May, scientists successfully performed gene correction in human fibroblasts, which are cells found in skin.

 “CEP290 defects can cause severe vision loss or blindness at birth, so the Editas project targets a critical need,” says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness. “We are very pleased that another player is addressing CEP290.”

CEP290-associated LCA is challenging to treat because the gene is too large for most delivery systems, namely adeno-associated viruses, or AAVs. They are being used in clinical trials for retinal-disease, gene-replacement therapies.

The Foundation is currently funding three projects to overcome the large-gene challenge. One effort, at the University of Florida, involves delivery of CEP290 to the retina using two AAVs.  Another supports research at the University of Iowa for using a high-capacity lentivirus to deliver CEP290. And Alejandro Garanto, Ph.D., at the Radboud University Medical Centre in the Netherlands, is developing what are known as antisense oligonucleotides, or AOs, to correct the defective messaging that occurs with certain types of CEP290 mutations.

As an alternative to these approaches, Editas uses cut-and-paste technology known as CRISPR/Cas9 to correct defective copies of CEP290. (The long-hand for this technology is: Clustered, Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9.) CRISPR, which comes from the immune system in strep bacteria, locates the region in the gene that needs correction. Cas9 is the molecular scissors that cuts out the mutation.

“While gene-editing systems like CRISPR/Cas9 are not as developed as gene-replacement technologies, we are excited about their potential,” says Dr. Rose. “In addressing the diverse and complicated world of inherited retinal diseases, we definitely need multiple tools in our tool belt.” 

The Foundation is also funding Donald Zack, M.D., Ph.D., Johns Hopkins University, who is developing a CRISPR/Cas9 therapy for autosomal dominant retinitis pigmentosa.