What is CRISPR-Cas9?
Imagine you’re typing up your mother’s famous lasagna recipe. After you finish, you notice that instead of typing 3 C of marinara sauce, you typed 30 C. You quickly realize your one keystroke error would result in a very saucy lasagna that would not make your mother proud. So before you print, you drag your mouse to the error and delete the zero. Your recipe is saved and there’s no need to call for delivery. The same cutting and editing principle is behind CRISPR-Cas9, the revolutionary genetic editing tool that manyhave billed as the next Nobel Prize winner. If we think of our genetic material as a recipe for our bodies, we know that genetic mutations (or errors in the lasagna recipe), can result in the development of deadly genetic disorders such as Huntington’s or Cystic fibrosis. With your lasagna recipe error, you simply highlight the error with your computer mouse, right click and “cut” the error out of the recipe. CRISPR-Cas9 works the same way, by using a guide molecule (computer mouse) and an enzyme called Cas9 that can “cut” out genetic material (cut function in Word). This tool can quickly and efficiently remove the part of a gene that is causing a disease.
CRISPR & ALS
Since its explosion onto the market five years ago, CRISPR has been used in a wide range of sectors, allowing scientists to treat hearing loss in mice and grow bigger tomatoes for your summertime BLTs. But by and large, the greatest implications of CRISPR has been in the medical sector. The therapeutic potential of CRISPR is vast; scientists have used CRISPR to target several diseases, including several that have an underlying genetic causes like amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease with no cure. Recently, researchers treated a mouse model of ALS using CRISPR to target motor neurons in the spinal cord. They were specifically interested in a gene called SOD1, as mutations in this gene are responsible for 20% of all genetically-caused ALS cases. CRISPR disabled the mutated SOD1 gene in mice with ALS, resulting in increased longevity, improved motor function, and decreased muscle atrophy. While the genetic editing didn’t cure ALS in these mice, this study is part of the growing evidence of successful CRISPR use in treating diseases that affect the brain and spinal cord.
Genetic Editing: Coming to a clinical trial near you
With astonishing success in animal models, the race is on to move CRISPR into clinical trials. Partnering with Vertex Pharmaceuticals, CRISPR Therapeutics announced it will begin a clinical trial in Europe testing its gene editing therapy, CTX001, for patients with β-thalassemia, a deadly blood disease. The company also plans to submit an application to treat sickle cell disease in a U.S. clinical trial. In the U.S., doctors at the University of Pennsylvania are planning to enroll up to 18 patients fighting various forms of cancer for their Phase 1 clinical trial using CRISPR to genetically alter immune cells to better destroy cancer cells. In both of these clinical trials, scientists will remove blood from the patient and use CRISPR to genetically alter the blood cells, These new (and hopefully improved) cells will then be injected back into the patient and the edits will be distributed (or something like that). This ex vivo approach is less risky than injecting CRISPR directly into the bloodstream, which could cause an immune reaction. Using genetic editing to treat medical conditions doesn’t come without ethical and methodological concerns. One of the biggest safety concerns is the risk of off-target effects, where CRISPR could accidentally cut the DNA in the wrong location, potentially resulting in a benign mutation, or activating a cancer-causing gene. Nevertheless, with three CRISPR clinical trials in the works, genetic editing may one day be the key to treating these debilitating diseases.