CRISPR Prevents Beginning Stage of Vision Loss – Genetic Engineering & Biotechnology News
Posted: July 31, 2017 at 6:41 am
Those who keep track of current science news, scientists and nonscientists alike, have probably found themselves asking aloud very often is there anything CRISPR cant do? So far, it would seem the answer to that question is "no" as a team of investigators from Schepens Eye Research Institute of Massachusetts Eye and Ear have found a new area for CRISPR interventionangiogenesis of the retina. The scientists were able to prevent the development of angiogenesis in mice, which often causes vision loss and blindness and is a feature of several degenerative eye conditions, including proliferative diabetic retinopathy (PDR), wet age-related macular degeneration (AMD), and retinopathy of prematurity (ROP).
Findings from the new studypublished recently in Nature Communications in an article entitled Genome Editing Abrogates Angiogenesis In Vivocould potentially lead to the development of new therapies for eye conditions marked by pathological intraocular angiogenesis.
"We know that vascular endothelial growth factor receptor 2 (VEGFR2) plays an essential role in angiogenesis," explained senior study investigator Hetian Lei, Ph.D., assistant professor of ophthalmology at Harvard Medical School and assistant scientist at Schepens Eye Research Institute of Massachusetts Eye and Ear. "The CRISPR/Cas9 system can be utilized to edit the VEGFR2 gene, preventing intraocular pathological angiogenesis."
Even with the success of several VEGF-inhibiting agents in reducing neovascular growth and lessening vascular leakage in retinal diseases such as PDR and AMD, several therapeutic challenges remainnamely a need for sustained treatment and a modality to treat the sizeable number of patients who do not respond to anti-VEGF therapies.
Clinically, many vision disorders present when blood vessels within the retina 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. In the current study, the investigators decided to use the CRISPR/Cas9 system to target the VEGFR2 gene in mice, with the hope of preventing the start of angiogenesis.
...we report that a system of adeno-associated virus (AAV)-mediated clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9) is used to deplete VEGFR2 in vascular endothelial cells (ECs), whereby the expression of SpCas9 is driven by an endothelial-specific promoter of intercellular adhesion molecule 2, the authors wrote. We further show that recombinant AAV serotype 1 (rAAV1) transduces ECs of pathologic vessels, and that editing of genomic VEGFR2 locus using rAAV1-mediated CRISPR/Cas9 abrogates angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization.
Amazingly, the research team was able to prevent retinal angiogenesis in the preclinical models using only a single injection of the AAV/CRISPR therapy. The investigators were excited by their findings and are optimistic that their study will lead to future strategies using genome-editing tools to vision loss disorders.
"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," Dr. Lei concluded. "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."
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CRISPR Prevents Beginning Stage of Vision Loss - Genetic Engineering & Biotechnology News
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