Professors Jennifer Doudna, PhD, and Emmanuelle Charpentier, PhD, were the runners-up for TIME magazine’s Person of the Year in 2016, but they more than made up for that slight this month when they won the Nobel Prize in Chemistry 2020 for their development of clustered regularly interspaced short palindromic repeats (CRISPR)-mediated gene editing — the first science Nobel ever won by 2 women. CRISPR-Cas9 is an antiviral defense mechanism that has been modified as a genetic engineering technique where particular genetic sequences can be cut at a desired location, allowing removal of existing genes or addition of new ones.

Dr. Doudna, at the University of California–Berkeley, discovered that the CRISPR-associated (Cas) protein found in the Streptococcus pyogenes CRISPR immune system (SpCas9) acts like a scissors to attack the DNA of viral particles, preventing infection of the bacteria. After meeting Dr. Doudna in 2011, Dr. Charpentier of the Max Planck Institute found that they could use Cas9 and different noncoding RNA to program, cut, and even edit any DNA sequence they desired. The CRISPR-Cas9 system can be used to edit the genome of any organism.

The patent for the CRISPR system was filed at almost the same time by 2 groups, UC Berkeley and the Broad Institute, which is affiliated with MIT and Harvard. The Broad Institute demonstrated its technique months after Drs. Doudna and Charpentier published their techniques. Interestingly, the patent was granted to the Broad Institute, which has since prevailed on appeal. UC Berkeley was granted a patent that covers the general technique. In Europe, the situation is just as complex, with the patent likely going to UC Berkeley and Max Plank Institute. So, who owns this space is still unclear.

In this issue, we explore the use of gene therapy in the treatment of retinal diseases. Two companies are using adenoviral vectors (AAV) to deliver genes that makes cells produce either a ranibizumab-like protein or an aflibercept-like protein. Numerous companies are using this same technique to target monogenetic inherited retinal degenerations. But one company is using viral vectors to deliver CRISPR-Cas9 to genetically treat Leber congenital amaurosis. This very precise gene editing is very exciting. Researchers at Massachusetts Eye and Ear Infirmary have already used AAV-CRISPR-Cas9 to edit genomic VEGFR2 in ocular vascular endothelium using specific promoters to prevent angiogenesis in mouse oxygen-induced retinopathy and laser-induced choroidal neovascularization models. Other laboratories have been able to suppress VEGF-A production in animal models, and so the race to bring this to the clinic is on. RP