Gene Editing, Gene Therapy, and RNA Medicines: Three Different Ways to Change an Outcome

On 8 December 2023, the US Food and Drug Administration did something it had never done before: it approved a medicine made with CRISPR, the gene-editing tool that had won its inventors a Nobel Prize only three years earlier. The product, Casgevy, treats sickle cell disease—an inherited blood disorder that, according to the FDA, affects about 100,000 people in the United States. On the same day, the agency approved a second gene therapy for the same disease, Lyfgenia, built on an entirely different technology.

Two medicines, one disease, two ways of rewriting biology. That pairing makes December 2023 a useful vantage point for understanding the wider field of genetic medicine—which, despite being lumped together in headlines, contains at least three distinct strategies for changing a patient’s outcome.

What Casgevy actually does

Sickle cell disease is caused by a change in the gene for haemoglobin, the oxygen-carrying protein in red blood cells. The faulty protein can make red cells stiff and crescent-shaped, and they can block blood vessels, causing episodes of severe pain known as vaso-occlusive crises, as well as organ damage.

Casgevy does not fix that faulty gene directly. Instead, it exploits a quirk of human development. Before birth, we make a different form of the protein, fetal haemoglobin, which is normally switched off after infancy. Casgevy uses CRISPR/Cas9 to edit a patient’s own blood-forming stem cells in a laboratory, disrupting a genetic switch (a regulatory region of a gene called BCL11A) that keeps fetal haemoglobin turned off. The edited cells are then infused back into the patient, where they can produce red cells rich in fetal haemoglobin.

The evidence behind the approval was specific. In the FDA’s summary, 29 of 31 evaluable patients in the main study (93.5%) went at least 12 consecutive months without severe vaso-occlusive crises during a 24-month follow-up period. The treatment is also demanding: before the infusion, patients receive high-dose chemotherapy (called myeloablative conditioning) to clear space in the bone marrow, and common side effects included low platelet and white blood cell counts, mouth sores and fever with low white cell counts.

The story did not stop there. In January 2024, the FDA approved Casgevy for transfusion-dependent beta thalassaemia, another inherited blood disorder. And in July 2026, the agency extended its use to patients as young as two with either condition.

Casgevy did not prove that gene editing is easy. It proved that, done carefully, it can be a medicine.

Three different ways to change an outcome

A helpful way to picture genetic medicine is to think of a cookbook. DNA is the master recipe book, kept safe in the cell’s nucleus. RNA is the photocopied page the kitchen actually works from. Proteins are the dishes. You can intervene at each level.

1. Gene therapy: add a working copy of the recipe

The FDA describes gene therapy as a technique that modifies a person’s genes to treat or cure disease—by replacing a faulty gene with a working one, switching off a harmful gene, or introducing a new or modified gene. Often a harmless, engineered virus is used as a delivery vehicle, or vector.

An early landmark was Luxturna, approved by the FDA in December 2017 for people with inherited retinal disease caused by mutations in both copies of the RPE65 gene. It uses an adeno-associated virus (AAV) to deliver a working copy of the gene to cells in the retina. Lyfgenia, the other sickle cell therapy approved in December 2023, also adds genetic material—using a lentiviral vector, derived from a different virus family, to give a patient’s stem cells a modified haemoglobin gene. Its label carries a boxed warning about the risk of blood cancer, with lifelong monitoring required.

2. Gene editing: change the recipe itself

Gene editing makes targeted changes to the DNA already in a cell. CRISPR/Cas9 works like molecular scissors guided to a precise address; newer variants such as base editing can swap a single DNA letter for another without fully cutting both strands of the DNA.

The first published human test of the approach behind Casgevy appeared in the New England Journal of Medicine in 2021, describing two patients—one with sickle cell disease and one with beta thalassaemia—who no longer needed transfusions more than a year after treatment. That was proof of principle. Larger trials, and the FDA’s review, came later.

In May 2025, the National Institutes of Health described an even more individual case: an infant with a rare metabolic disorder, CPS1 deficiency, who received a base-editing therapy designed for his specific mutation and delivered to the liver in fatty nanoparticles, roughly six months after diagnosis. Researchers reported encouraging early signs—but this was a single patient, and they stressed the need for long-term follow-up to establish safety and effectiveness.

3. RNA medicines: change the photocopy, not the book

RNA medicines leave DNA untouched. As MedlinePlus explains, they change whether or how a gene’s instructions are used to make a protein. Small interfering RNA (siRNA) drugs, for example, tag a specific RNA message for destruction, so less of a harmful protein is made. Antisense oligonucleotides are short strands that bind RNA and alter how it is processed.

In 2018, the FDA approved patisiran (Onpattro), the first siRNA drug, for a rare inherited disease in which a misfolded protein called transthyretin builds up in nerves and other organs. Because RNA medicines don’t permanently alter the genome, their effects typically fade unless treatment is repeated—which can be a drawback or a safety feature, depending on the disease.

Plain English: Gene therapy adds genetic instructions. Gene editing rewrites existing ones. RNA medicines turn the volume up or down on instructions without changing them.

How the three compare

• Permanence. Gene editing aims for lasting change; many gene therapies are intended to be long-lasting; RNA drugs usually need repeat doses.
• Delivery. All three must reach the right cells. Some treatments edit cells outside the body (ex vivo) and return them, as with Casgevy; others are delivered inside the body (in vivo), often to the liver or eye, which are easier to reach.
• Reversibility. An RNA drug can be stopped. An edit to DNA cannot simply be undone, which is why regulators scrutinise possible unintended edits elsewhere in the genome.
• Stage. Each approach now has approved products for specific conditions, alongside many candidates still in clinical trials or preclinical research.

What Casgevy proves—and what it doesn’t

Casgevy shows that CRISPR editing can clear the bar of a full regulatory review. It does not show that gene editing will work for every genetic disease, or that the hard parts are solved. Treatment requires collecting a patient’s stem cells, manufacturing a personalised product, and chemotherapy conditioning with serious side effects, delivered in specialised centres. Long-term durability and safety will only be known after years of follow-up. And much of the global burden of sickle cell disease falls in regions with the least access to such complex care.

That is why the most-watched frontier is delivery: getting editors and genes into the right cells inside the body, without chemotherapy and without a manufacturing plant for every patient. If you want to evaluate the next announcement, our guide on how to read a biotech breakthrough and our explainer on what trial phases really mean are good places to start—and our primer on decoding the genome explains how doctors find the genetic target in the first place.

What to watch next

• Long-term follow-up data on patients treated with approved gene and editing therapies.
• In vivo editing trials that could avoid chemotherapy conditioning.
• Whether rapid, personalised “N-of-1” therapies can move from single cases to a repeatable regulatory pathway.
• Access, manufacturing and cost questions as more genetic medicines reach the market.

New to the vocabulary? Our glossary covers every term in this piece.