It’s 2020: the year of the plague, of wildfires and protests, of missed graduations and goodbyes.
2020 was supposed to be different. The start of a new decade, it was going to be defined by game-changing elections, scientific breakthroughs, and good times. After all, it was the year when the visually impaired were finally going to have “2020” vision, as the joke goes. Instead, it’s been marked by crisis after crisis—least of all, a global pandemic that’s left many holed up at home. With the current flood of panic and pressure, it’s hard to see anything positive about what’s happening right now. And yet, in the midst of all the turmoil, science has continued to move forward. In the past few months, scientists have developed and tested a new treatment for blindness, creating stunning breakthroughs along the way.
Sight is one of the most important senses, affecting how we interact with our environment. However, it is also one of the most vulnerable, with an estimated 2.2 billion people suffering from blindness or visual impairment worldwide (1). For some, poor sight is just a result of age-related degeneration, but for at least 2 million people across the globe, it is the result of genetic disorders (2). It is for this reason that the eye has become the focus of numerous gene therapies by scientists.
Gene therapies operate by attempting to remediate the effects of mutated genes, either through altering them or introducing new ones. Over the years, gene therapy has grown in popularity to the point that a few years ago, the FDA approved the first drug of its kind, Luxturna, to treat the Type 2 Leber congenital amaurosis (LCA), one of the leading causes of childhood blindness (3).
In LCA Type 2, a mutation occurs in a gene called RPE65, leading to an inability to capture and transmit light to the brain and, therefore, see. Using Luxturna, however, scientists have been able to insert a healthy copy of the gene into the retina to reenable sight. Unfortunately, Luxturna has only been able to serve as a temporary fix, largely because of problems with efficiently delivering the DNA (4). However, scientists have recently found a solution—CRISPR.
Developed in the past decade, CRISPR and its associated protein, Cas9, have become the newest tools in gene editing. CRISPR works by essentially finding a target gene and making a cut in it, allowing for additions, deletions, or customized replacements of DNA, making it a simple, yet powerful tool. In the past, CRISPR has only been used to edit genetic material taken from the body, which is then reinfused. However, in March, it was announced that, for the first time, CRISPR was inserted into the human body.
For this occasion, scientists set out to treat LCA Type 10, a form of LCA caused by a mutation in the gene CEP290. Instead of using the general method of inserting a healthy gene as in Luxturna, scientists opted to use CRISPR to directly edit the gene, because CEP290 was too large for transmission. As a result, CRISPR was administered to a patient as a part of a clinical trial called BRILLIANCE that will later test its efficacy and safety as a treatment for 18 patients (5).
Although the results aren’t clear yet, BRILLIANCE’s test with inserting CRISPR has been heralded as a significant advancement in gene therapy. Gone are the days of playing around with and editing the DNA of cells in petri dishes. Now, scientists have the capability to edit the DNA directly in patients. Better yet, gene-editing through CRISPR promises a permanent fix by altering the DNA, in contrast to the conventional gene therapy strategies such as in Luxturna. Although significant concerns remain over CRISPR’s ethics and safety, especially pertaining to its use in humans, the technology forebodes the possibility of new treatments aimed at the multitude of genetic diseases that plague humans.
2020 might not be the year people hoped for—not the year of celebrations, of festivities, of gains and goals. But it can still be the year of 2020 vision. If not now, then surely soon.
References:
- “WHO Launches First World Report on Vision.” World Health Organization, World Health Organization, 8 Oct. 2019, www.who.int/news-room/detail/08-10-2019-who-launches-first-world-report-on-vision.
- Moshiri Associate Professor of Ophthalmology, Ala. “Hundreds of Genes Linked to Blindness Could Lead to New Therapies.” The Conversation, 20 Feb. 2019, theconversation.com/hundreds-of-genes-linked-to-blindness-could-lead-to-new-therapies-108978.
- “FDA Approves Novel Gene Therapy to Treat Patients with a Rare Form of Inherited Vision Loss.” U.S. Food and Drug Administration, FDA, 18 Dec. 2017, www.fda.gov/news-events/press-announcements/fda-approves-novel-gene-therapy-treat-patients-rare-form-inherited-vision-loss.
- O'Hare, Ryan. “LCA Gene Therapy Unable to Stop Long-Term Sight Loss.” Association of Optometrists (AOP) - Homepage, 5 May 2015, www.aop.org.uk/ot/science-and-vision/research/2015/05/05/lca-gene-therapy-unable-to-stop-long-term-sight-loss.
- Ledford, Heidi. “CRISPR Treatment Inserted Directly into the Body for First Time.” Nature News, Nature Publishing Group, 5 Mar. 2020, www.nature.com/articles/d41586-020-00655-8.