World’s First Approved CRISPR Therapy: A Comprehensive Guide

CRISPR is a revolutionary gene-editing technology that allows scientists to make precise changes in the DNA of living cells. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are sequences of DNA that can be targeted by a special enzyme called Cas9. By using a guide RNA molecule that matches a specific region of DNA, Cas9 can cut and edit the DNA as desired.

What is Casgevy and how does it work?

Casgevy, also known by its brand name Exa-cel, is the world’s first approved CRISPR therapy. It is a treatment for two inherited blood disorders: sickle cell disease and transfusion-dependent beta-thalassemia. These disorders are caused by mutations in the gene that codes for beta-globin, a protein that forms part of hemoglobin, the molecule that carries oxygen in red blood cells.

Casgevy works by extracting stem cells from the patient’s bone marrow and editing them with CRISPR-Cas9 to insert a gene that produces fetal hemoglobin, a form of hemoglobin that is normally present only in fetuses and infants. Fetal hemoglobin can compensate for the defective beta-globin and prevent the red blood cells from sickling or losing their ability to carry oxygen. The edited stem cells are then infused back into the patient, where they can produce healthy red blood cells for life.

What are the benefits and risks of Casgevy?

Casgevy has shown remarkable results in clinical trials, curing some patients of their symptoms and reducing their need for blood transfusions. According to the UK’s Medicines and Healthcare Products Agency (MHRA), which approved Casgevy on Nov. 16, 2023, the therapy eliminated severe vaso-occlusive crises — painful inflammatory attacks — in 28 out of 29 trial participants with sickle cell disease. It also increased hemoglobin levels and reduced transfusion requirements in patients with beta-thalassemia.

Casgevy is a one-time treatment that could potentially offer a lifelong cure for these debilitating diseases. However, it is also a complex and costly therapy that requires specialized facilities and expertise to administer. The therapy involves chemotherapy to destroy the patient’s existing bone marrow before transplanting the edited stem cells, which carries risks of infection, bleeding, and graft-versus-host disease. The long-term safety of Casgevy is also unknown at this point, as there is a possibility that CRISPR-Cas9 could introduce unwanted mutations or trigger cancer in the edited cells. Vertex Pharmaceuticals and CRISPR Therapeutics, the companies that developed Casgevy, will be enrolling patients from earlier trials in a 15-year safety study to monitor any adverse effects.

What are the implications and challenges of Casgevy?

Casgevy is a historic milestone for gene therapy and biotechnology, demonstrating the power and potential of CRISPR-Cas9 to treat genetic diseases. It is also a testament to the rapid development of this technology, which was invented only 11 years ago by Jennifer Doudna and Emmanuelle Charpentier, who won the Nobel Prize in Chemistry in 2020 for their discovery.

However, Casgevy also faces several challenges before it can reach more patients who need it. The therapy is expected to be very expensive, with some estimates ranging from $1 million to $2 million per patient. The availability and accessibility of Casgevy will depend on how health systems and insurers will cover its cost and how regulators in other countries will approve it. The U.S. Food and Drug Administration (FDA) is expected to make its decision on Casgevy by December 2023 for sickle cell disease and by March 2024 for beta-thalassemia.

Another challenge is the limited capacity and infrastructure to deliver Casgevy to patients who are eligible for it. The therapy requires specialized centers that can perform bone marrow transplants and gene editing procedures, which are not widely available in many parts of the world where sickle cell disease and beta-thalassemia are prevalent. Moreover, some patients may prefer to wait or opt for alternative treatments, such as gene therapies that do not involve CRISPR-Cas9 or gene editing at all.

Casgevy is an exciting breakthrough that opens new possibilities for curing genetic diseases with CRISPR-Cas9. However, it also raises ethical, social, and economic questions that need to be addressed as this technology advances.