CRISPR/Cas9 Genetic Medicines

In December 2023, the FDA approved the first CRISPR/Cas9 genetic medicine, Casgevy, to treat sickle cell anemia. It ushered in a new era of medicine. 

To understand why, consider how Casgevy works. Sickle cell disease is caused by a mutation in hemoglobin that creates crescent-shaped red blood cells. These restrict blood flow and produce crippling pain and organ damage. It shows up when children stop making fetal hemoglobin at about six months. 

Casgevy works by modifying blood stem cell DNA. It does not eliminate the sickle cell mutation. Instead, it restarts fetal hemoglobin production, which suppresses the formation of sickle cells. 

Regulators have approved more than 30 genetic medicines since 2017. Most of them use proteins, which are slow and expensive to build, to make DNA modifications.

Casgevy, on the other hand, uses a technology called CRISPR/Cas9. Instead of creating proteins, it synthesizes RNA "guides" from roughly 20 simple molecules. These guides deliver the Cas9 protein to the precise segment of the DNA it needs to modify. 

This makes genetic medicines more practical. It also changes how researchers study genetic diseases. Instead of taking two or three years to modify mouse DNA to mimic a disease, they can do it in weeks. CRISPR/Cas9 also speeds up validating certain types of drugs. 

While biologists discovered CRISPR/Cas9, biomedical engineers transformed it into practical technology. They developed several ways to deliver the RNA to cells, engineering lipids and viruses to target specific tissues and release Cas9 when they get there. Since viruses cannot contain an entire Cas9 protein, they developed a way to split the protein in half and reassemble it within the cell.

Biomedical engineers fused CRISPR's two original RNA guides into a single molecule and modified it so it resists the cellular enzymes that try to destroy it. They also continue to develop Cas9 variants that are more selective. 

CRISPR/Cas9 promises to transform medicine both in the hospital and in the lab. Biomedical engineers have played a vital role making this possible.