September 3, 2024

Lily Sharkey  

12th Grade

Dominican Academy

The first Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) therapy to be approved by the Food and Drug Administration (FDA) offers new hope for 20 million people across the world who live with sickle cell disease (SCD). Friday, December 8, 2023 marked the beginning of a new era of treatment for SCD patients dealing with chronic pain, vaso-occlusive crises, and frequent hospitalizations. But what is CRISPR therapy and what does it mean for the future of chronic illness treatments?

Just like humans, bacteria can be infected by viruses called bacteriophages which inject the bacteria with their viral DNA. As they evolve, bacteria create defense mechanisms to protect themselves from invasive bacteriophages, one such mechanism being Clustered Regularly Interspaced Short Palindromic Repeats. These CRISPR-Cas defense systems are found in 50% of known bacteria and almost all archaea species; CRISPR-Cas systems protect these organisms from repeated infection from bacteriophages by creating a memory of how to defend against the bacteriophage. CRISPR uses RNA to guide cutting enzymes to a specific location on a strand of DNA and remove the viral gene to end the infection; in the realm of biotechnology, these systems create the foundation for genome editing technology that can be used to permanently alter the genes of an organism. CRISPR was first used in 2013 by the Broad Institute’s Zhang Laboratory to edit the genome of mouse and human cells. 

Until recently, bone marrow transfers were the only way for patients with SCD to live without symptoms. This transplant gives patients an influx of healthy red blood cells from a donor match. However, finding the right match is rare and the transplant comes with its own risks. Most matches are siblings, who carry similar immune system genes, but only 15% of patients will have a sibling donor. Even after the transplant, there are risks the new cells may be rejected by the body or attack the body’s organs. Using a patient’s own cells reduces this risk - that is where CRISPR comes in.

Both treatments are administered as a one-time stem cell transplant infusion. Stem cells are acquired from a patient before being edited; before receiving the edited cells back, the patient must undergo a form of high-dose chemotherapy called myeloablative conditioning to remove cells from the bone marrow to be replaced with those modified cells. According to a study released by the FDA, 93.5% of patients treated with Casgevy who experienced “two protocol-defined severe VOCs during each of the two years prior to screening” had no severe VOCs for at least twelve consecutive months during a 24-month follow-up period. All patients had successful engraftment, meaning no patients rejected the modified stem cells. For patients between twelve and 50 years old who were treated with Lyfgenia, 88% of patients experienced complete resolution of VOEs (VOE-CR) during a six to eighteen-month period after infusion. However, the FDA states that some patients treated with Lyfgenia have incurred hematologic malignancy (blood cancer). 

For patients with SCD, these new gene therapy treatments promise a hopeful future. Victoria Gray, the first patient to enroll in the clinical trial, says that she has been set free from a life of crippling pain and can now enjoy her time with her family. Jimi Olaghere, another patient in the trial, says that before treatment, “sickle cell disease dominated every facet of my life. Hospital admissions were so regular that they even had a bed reserved for me”. Now, Olaghere can spend valuable time with his children. “Gene therapy has given me the ability to take full control of my life”, he said. “I can chase to the proverbial sunset and write novels and even dance in the rain without a care in the world”.