The World’s First CRISPR/Cas9 Gene Editing Therapy

By: Adhrith Vutukur

From MCR’s Washington Chapter

From Unsplash

On December 2023, the Food and Drug Administration approved the worlds first CRISPR/Cas9 gene editing therapy to treat sickle cell disease. The drug, called Casgevy, was approved for use in patients 12 or older. 

CRISPR/Cas9

Before discussing Casgevy, it’s important to understand the molecular scissors behind this revolutionary drug. CRISPR/Cas9 is a gene editing technology discovered relatively recently. It makes it possible to edit the genome relatively cheaply and simply compared to other gene editing methods. CRISPR/Cas9 has two components: a guide RNA to match a desired target gene, and Cas9 which is an endonuclease that causes a double-stranded DNA break, allowing modifications to the genome. From the time it was discovered, many scientists saw this gene editing technology's potential to treat disease caused by single gene mutations, such as sickle cell disease. In Casgevy, scientists used the CRISPR/Cas9 system to edit the point mutation responsible for sickle cell disease in some people. 

Sickle Cell Disease

Sickle Cell Disease (SCD) is the most common inherited blood disorder which affects peoples red blood cells. More specifically, patients with SCD have a genetic mutation which causes a protein called hemoglobin, found in red blood cells, to be abnormal. The abnormal hemoglobin protein can cause red blood cells in patients to change shape from a round shape to a crescent shape. It also causes red blood cells to become rigid, lack flexibility, and stick together. These abnormal red blood cells can block blood flow thus preventing blood and oxygen from getting to vital organs and tissues. SCD can also cause a shortage in red blood cells thus leading to anemia.

Casgevy

As mention earlier, Casgevy is the first CRISPR-based medicine to receive the greenlight from the FDA. This marks a huge step forward in the field of gene editing therapies. Casgevy works by editing the DNA of a patients stem cells, which are responsible for producing red blood cells, thus stoping the stem cells from producing abnormal red blood cells found in SCD. 

Casgevy is technically a one-time treatment, but there are many steps before and after the treatment which are essential for its success. First, patients must get multiple bood transfusions over a span of 3 to 4 months. Next, stem cells are extracted from their bone marrow and sent to a lab where they are edited using CRISP/Cas9. Then, chemotherapy is used to ensure no flawed stem cells remain in the patients bone marrow. Only at this point can doctor reinfuse stem cells into the patients body. After the treatments, patients must spend 1-2 months in a hospital to recover. Many of the trail patients recall the prcocess before the treatment to be extremely difficult, even making them regret their decision to join the trial. Luckily, after the CRISPR treatment, most patients felt much better and were able to start living a normal life, something they could only dream of before the treatment. Although this therepy is a revolutionary step forward in treating genetic diseases, at the moment casgevy is inaccessible for most due to its expensive cost of $2.2 million per patient. This price does not even include the cost of care associated with treatment. 

Future

Although casgevy has been successful thus far, it’s unclear what its long-term effects will be. Scientist will have to wait and observe the patients to truly understand this therapies long-term effects. At the moment, the biggest fear is that casgevy may cause unintended health conditions such as blood cancer in patients. Because of this, long term follow-up is going to be crucial for casegevy. 

1. Cleveland Clinic. "Sickle Cell Disease (SCD): Types, Symptoms & Causes." Cleveland Clinic, 28 Oct. 2022, https://my.clevelandclinic.org/health/diseases/14241-sickle-cell-disease-scd.

1. National Library of Medicine. "What Is CRISPR/Cas9?" PubMed Central, National Institutes of Health, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760970/.

1. Wetsman, Nicoletta Lanese. "The First CRISPR Therapy Approved in the U.S. Will Treat Sickle Cell Disease." Science News, 5 Sep. 2023, https://www.sciencenews.org/article/first-crispr-therapy-approved-sickle-cell-disease.