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Editing Out Disease

Using genome editing to prevent eye damage

Fluorescein angiography images demonstrate editing genomic VEGFR2 with CRISPR-Cas9 in mice that promotes regression of choroidal neovascularization 14 days following laser-injury. Image: Xionggao Huang

A team of Harvard Medical School researchers from the Schepens Eye Research Institute of Massachusetts Eye and Ear has successfully prevented mice from developing excessive growth of blood vessels in the retina—the sensory tissue at the back of the eye—using gene-editing techniques with CRISPR-Cas9.

Excessive growth of blood vessels, or angiogenesis, causes vision loss and blindness and is a feature of several degenerative eye conditions, including proliferative diabetic retinopathy, wet age-related macular degeneration and retinopathy of prematurity.

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In a report recently published in Nature Communications, the researchers present a novel gene-editing technique to prevent retinal angiogenesis, which could lead to the development of new therapies for eye conditions marked by this symptom. 

There has been progress in the development of preventative therapies and treatments for degenerative eye conditions, such as the success of vascular endothelial cell growth factor (VEGF) inhibiting agents that reduce blood vessel growth and leakage in retinal diseases.

However, several therapeutic challenges remain—namely a need for sustained treatment and a method to treat the significant number of patients who do not respond to anti-VEGF therapies.

“We know that vascular endothelial growth factor receptor 2 (VEGFR2) plays an essential role in angiogenesis,” said corresponding author Hetian Lei, HMS assistant professor of ophthalmology and an assistant scientist at Schepens.

“The CRISPR-Cas9 system can be utilized to edit the VEGFR2 gene, preventing intraocular pathological angiogenesis,” Lei said.

A feature of various eye diseases, pathological intraocular angiogenesis presents clinically when blood vessels in the retina (the structure in the back of the eye that senses and perceives light) begin to grow new, abnormal blood vessels on the surface of the retina.

As the damage progresses, these vessels can leak, rupture or cause retinal detachment leading to impaired vision.

CRISPR-Cas9 is a powerful new technology that can target and edit certain aspects of the genome or the complete set of genetic material of an organism.

In the Nature Communications report, study authors used an adeno-associated virus to deliver genomic edits to target VEGFR2, a critical protein responsible for angiogenesis. A single injection of this therapy was able to prevent retinal angiogenesis in preclinical models. 

“As this genomic editing gains traction in virtually all medical fields, we are cautiously optimistic that this powerful tool may present a novel therapy to prevent vision loss in eye disease marked by intraocular pathological angiogenesis,” said Lei.

“While further study is needed to determine safety and efficacy of this approach, our work shows that the CRISPR-Cas9 system is a precise and efficient tool with the potential to treat angiogenesis-associated diseases,” Lei added. 

This research study was supported by National Institutes of Health/National Eye Institute grants R01EY012509 and P30EY003790.

Adapted from a Mass. Eye and Ear news release.