America’s healthcare industry achieved a historic milestone last month when the Food and Drug Administration approved the country’s first use of two gene-editing therapies — one of which uses CRISPR technology that allows scientists to edit the human gene. The therapies, Casgevy and Lyfgenia, will act as functional cures for sickle cell disease.

“This technology allows you to use the patients' own cells and tissues, fix them, and put them back in, which is remarkable. The number of genetic diseases and other types of disorders we could treat with this is amazing,” says biologist and School of Health and Behavioral Sciences Director Kirsten Hokeness, Ph.D., noting that the treatments will be available for individuals ages 12 and older.

Hokeness explains that sickle cell disease is a genetic disorder that disproportionately affects Black and Latino populations and occurs when individuals inherit mutations of the gene for hemoglobin, a protein in red blood cells that carries oxygen throughout the body. Typically, a person’s red blood cells are round and flexible, which allows the cells to maneuver through blood vessels with ease; however, in sickle cell disease, red blood cells take on a sickle shape and become rigid.

“Sickle cells are really sticky, so they tend to get stuck in the blood vessels, which results in a decreased ability to transport oxygen throughout the body and causes individuals to feel fatigued,” Hokeness says, adding that many patients develop severe and debilitating pain when blood cells get lodged throughout the body, particularly in the joints.

According to the Centers for Disease Control and Prevention, sickle cell disease affects 100,000 Americans, and symptoms can start as early as five months old. Hokeness adds that parts of Africa have high levels of the disorder, and in part the trait is seen as advantageous since it protects people from malaria.

Prior to the FDA’s approval of Casgevy and Lyfgenia, Hokeness says treatment options included a drug that was not all that effective or a bone marrow transplant, which was problematic because it required a match.

Patients undergoing sickle cell treatment with Casgevy begin by having stem cells removed from their body. They then receive doses of chemotherapy to wipe out the remainder of hematopoietic stem cells that serve as a source for red blood cells. Meanwhile, in a lab, scientists take the removed stem cells and use Casgevy, which uses CRISPR technology, to find the de facto gene and edit it.

“Once the gene is located, the enzyme system enables clinicians to edit or replace the defective gene so the patient will no longer make the mutated version of hemoglobin and red blood cell shape and function can be restored,” Hokeness says, noting that afterward, patients are re-infused with their own cells.

The stem cell extraction and re-infusion process are the same for Lyfgenia, however, the delivery process of the genetic material is different. For Lyfgenia, scientists use an inactive virus to transport information to the cells so they can produce a modified version of the altered gene.

Overall, the process takes upwards of six months to a year. Hokeness adds that treatment costs between $2.2 and $3.1 million per patient, and 36 U.S. hospitals are currently authorized to use the new milestone treatments. While insurance coverage details need to be worked out, Hokeness notes that cost and equitable treatment is an issue since many sickle cell patients are on Medicaid and many countries with high rates of the disease are not wealthy.

According to the FDA, clinical trials demonstrated that Casgevy was 93.5 percent successful while Lyfgenia was 88 percent successful — promising results for a therapy that has the potential to treat and cure other genetic diseases, as well. Side effects may include lower levels of blood cell production, hypersensitivity reactions, and decreased clotting abilities during and after treatment.

“The long-term impacts are still yet to be seen, but this is a revolutionary step in using gene therapy to treat debilitating diseases, a tool that holds a lot of potential and promise for the future,” Hokeness says.