Updated on January 31, 2024.
In a groundbreaking move, the Food and Drug Administration (FDA) approved the first new therapy that utilizes the gene-editing technology known as CRISPR in December 2023. The drug called Casgevy, which was developed by Vertex Pharmaceuticals and CRISPR Therapeutics, is approved for the treatment of sickle cell disease—an inherited condition that causes severe pain, organ damage, and early death.
Sickle cell disease affects about 100,000 people in the United States and more than 20 million others around the world, primarily Black people. Until now, treatments for the condition, which may include monthly blood transfusions, only offer temporary relief and help prevent complications. They do not target the disease, itself. The landmark approval of Casgevy is a step forward for the management of sickle cell disease—and a monumental leap in the field of gene therapy.
What is CRISPR and how does it work?
There are some medical innovations that have transformed medicine—antibiotics, vaccines, anesthesia, and insulin among others. CRISPR is one more innovative technology with the potential to change the world.
CRISPR was co-invented by biochemist Jennifer Doudna and microbiologist Emmanuelle Charpentier, who began their collaboration in 2011 and won a Nobel Prize in 2020 for their research on gene editing.
Inspiration for the technology was born from a defense mechanism discovered in microbes, like bacteria. To protect themselves from virus, these tiny organisms capture little pieces of an invader’s DNA and store them as segments dubbed CRISPRs (or Clustered Regularly Interspersed Short Palindromic Repeats).
Then, if that invader returns, these CRISPRs are used to help slice up its DNA. This gave scientists the idea for a gene-editing tool with the potential to alter any section of DNA—not just in bacteria but also in people.
CRISPR is a technology that can be used to edit genes. Like a pair of scissors, it can find and cut (or alter) a piece of DNA within a cell. When DNA is cut, a cell tries to repair it. So, cells can be given new, healthy pieces of DNA to make these repairs. It can also be used to turn genes off or on without altering their sequence.
How does CRISPR help treat sickle cell disease?
Sickle cell disease is an inherited condition that changes the shape of red blood cells. Normally, these cells are round and flexible, but for those with the disease, they become crescent-shaped, rigid, and sticky. As a result, they can get stuck in blood vessels, which can be very painful and lead to infection. It can also reduce the supply of blood to vital organs.
Sickle cell disease is caused by a mutation in a gene that helps produce a protein in red blood cells called hemoglobin. But the mutation only affects adult hemoglobin, which the body produces after birth. Before birth, fetuses produce a different form of hemoglobin that is unaffected by the mutation.
The gene that codes for this fetal hemoglobin is turned off at birth. Using CRISPR, researchers are able replace the adult version by deactivating the gene that turns off the fetal hemoglobin, resulting in healthy red blood cells.
How CRISPR may transform medicine
The FDA approval of the world's first CRISPR treatment targets sickle cell disease but this is just the tip of the iceberg.
CRISPR is customizable. Three billion letters make up the human genome, and it can target nearly any segment of it. Theoretically, CRISPR could be used to cure any disease with a genetic origin by editing or swapping out harmful DNA variants for healthy ones.
Thus, it could treat and prevent a range of conditions, including cancer, AIDS, cystic fibrosis, Huntington’s disease, viral infections like COVID-19, high cholesterol, and infertility.
For example, scientists at Stanford University developed a version of CRISPR to cut and destroy the genetic material of the coronavirus that causes COVID-19, which would prevent it from infecting lung cells.
Researchers are also investigating the use of CRISPR to fix the harmful mutations that cause cancer, removing the specific genes and replacing them with the correct ones.
CRISPR could also be used to cut the viral DNA that the HIV virus inserts within the DNA of immune cells, destroying and eradicating the virus in its inactive form.
Some barriers and challenges remain
Over the past decade, gene editing technology has become faster, easier, and cheaper. But it’s still expensive.
Casgevy is the first step in bringing a CRISPR-based treatment to people with sickle cell disease, but this one-time therapy could cost more than $2 million per patient. Additionally, the healthcare infrastructure needed to administer the treatment is still limited, according to an article in Nature Biotechnology.
But sickle cell disease (SCD) will be the first focus of the Cell and Gene Therapy (CGT) Access Model, which is led by the Centers for Medicare & Medicaid Services’ (CMS’) Innovation Center. The goal of the model is to improve health outcomes, increase access to cell and gene therapies, and reduce health care costs for some of the most vulnerable populations. Roughly 50 to 60 percent of those living with SCD are enrolled in Medicaid. Hospitalizations and other health issues related to SCD cost nearly $3 billion per year, according to CMS. States may choose to begin participation anytime between January 2025 and January 2026.
Casgevy also gene-edits patients’ cells in a lab—not inside their body. Scientists are still working to figure out how to get CRISPR into human cells. And once they do, they will also need to ensure that it only edits the intended cells and does not alter any others, in a complication called “off-target” editing.
For now, editing cells outside of the body helps ensure CRISPER-based therapy doesn’t inadvertently edit other genes that are not responsible for disease. But editing genes outside the body requires patients to undergo high-dose chemotherapy to make room for the modified cells.
