An IV: nanoparticles that travel through the blood, reach the liver, and enter cells. Inside is a guide RNA that knows the address (the gene). ANGPTL3) and then there's Cas9, the protein that cuts DNA. Zac: the gene stops producing its protein. Cholesterol heals and drops. Forever, they hope. Or at least until we know more about what happens when you deactivate a gene in an adult human and let them roam the world with that modified DNA.
The Cleveland Clinic tested this preparation, called CTX310, on 15 patients between June 2024 and August 2025. LDL cholesterol: -49%. Triglycerides: -55%. The study It was published yesterday on New England Journal of MedicinePhase 2 is scheduled for late 2025.
The gene that nature has already turned off
Let's start from the context: about one in 250 people is born with the gene ANGPTL3 not working. No apparent negative consequences, but LDL cholesterol remains low throughout life, triglycerides are always under control and cardiovascular risk is reduced by 88% according to a 2006 study on NEJM.
ANGPTL3 normally inhibits enzymes that break down fats in the blood. Without it, the liver continues to remove excess cholesterol unhindered. It's like a manufacturing defect that improves the product.
The idea behind CTX310 is simple: replicate that natural mutation in people who don't have it. CRISPR Therapeutics They developed lipid nanoparticles that deliver the CRISPR-Cas9 gene editor directly into the liver. Once inside the liver cells, the system cuts the ANGPTL3 DNA at specific points. The cell attempts to repair the damage, but the gene remains permanently deactivated.
The trial involved 15 adults between the ages of 31 and 68, all with high cholesterol and triglycerides resistant to traditional medications. Five different doses of CTX310 were administered, ranging from 0,1 to 0,8 mg per kilogram of body weight. Before the infusion, corticosteroids and antihistamines were administered to prevent reactions. This was followed by a four-and-a-half-hour IV drip.
Result at the highest dose: ANGPTL3 reduced by 73% (maximum 89%), LDL cholesterol -49% (maximum 87%), triglycerides -55% (maximum 84%).
Data in hand, everything that happened
Three patients had mild reactions during the infusion: Back pain, nausea. The infusion was paused, antiemetics administered, and restarted. All patients completed the treatment. One patient developed a rash the next day, which resolved within 24 hours. Another patient had elevated liver enzymes even before treatment: they increased for a few more days (between 3 and 5 times the baseline value), then returned to normal within two weeks without any intervention.
And then there is the case that counts. One patient died 179 days after infusion. He had received the lowest dose, 0,1 mg/kg, which was virtually ineffective. He had pre-existing advanced cardiovascular disease. Investigators concluded that his death was not related to treatment. But when you edit the DNA of living humans, every event matters. Even if statistically irrelevant, even if clinically unrelated.
What's still missing?
Fifteen people. Sixty days of follow-up. Mostly men (87%). All white or Asian. No data on the actual duration of the effect beyond two monthsNo information about off-target mutations, unwanted DNA cuts elsewhere in the genome. The protocol provides for 15 years of monitoring, as the FDA requires for all CRISPR-based therapies.
Kiran Musunuru, researcher of the PennMedicine involved in CRISPR studies, said during the press conference that ANGPTL3 is a “very attractive target” precisely because people with natural mutations do not show problems.
But he also remembered what happened to Intellia TherapeuticsA patient died of severe liver damage just weeks after CRISPR treatment for transthyretin amyloidosis. Different gene, different population, but the question remains: how safe is it to edit the DNA of people with chronic but non-fatal diseases?
Comparison with what exists
Statins are inexpensive and work for many. anti-PCSK9 monoclonal antibodies They reduce LDL cholesterol by 50-60% but require injections every two weeks or a month. This is lifelong. Inclisiran, an RNA-mediated therapy, lowers cholesterol with two injections a year. The CTX310 promises a single infusion. And then nothing.
The real problem today? The price. Casgevy, the first approved CRISPR therapy (for sickle cell anemia and beta-thalassemia), costs $2,2 million per patient. CTX310 It will likely be in the same range. For familial hypercholesterolemia, currently managed with medications costing a few hundred euros a year, the cost-benefit calculation becomes complicated. Especially when long-term safety data is not yet available.
The potential market is huge. Tens of millions of people (40 million in the US alone) have elevated triglycerides or LDL cholesterol. CRISPR Therapeutics is already working on two other cardiovascular programs: CTX320 for lipoprotein(a) and CTX340 for hypertension. The idea is to build a whole line of genetic therapies for heart disease.
CRISP Cholesterol Cure: When Will It Arrive (Probably)?
Steven Nissen, cardiologist of the Cleveland Clinic and senior author of the study, said that Phase 2 will begin “soon, very soon,” quickly followed by Phase 3. The goal is to complete everything by the end of 2026.
“We are moving very quickly because this is a huge medical need,” he added.
The problem is that “very quickly” in the world of gene therapy still means years. Phase 3 will need to involve thousands of patients to demonstrate efficacy and, above all, safety in larger and more diverse populations. Regulators will want long-term data. Patients with severe familial hypercholesterolemia may not have years to wait, but those with moderately high cholesterol may not want to be among the first to try.
The question that remains
Editing an adult's DNA to prevent future diseases is different from treating a child with deadly sickle cell anemia. The risk-benefit threshold is shifting.
An infusion that could eliminate statins forever, a final cure for cholesterol, sounds good. But “forever” also means that you can’t go back, so you have to be careful. The ANGPTL3 gene will remain turned off for the rest of the patient's life. What if in ten years we discover that that protein was also used for something else?
People with the natural mutation are fine, it's true. But they were born that wayTheir bodies have always evolved to compensate. Turning off the same gene at 50, in a body that has functioned differently for half a century, might not be exactly the same. Mouse tests looked promising as early as 2021We now have the first human data. In a few years we will have the real answers.
Meanwhile, CTX310 is advancing. Phase 2 will begin by the end of the year. Cardiologists are starting to talk about "preventive gene editing" as if it were a normal drug category. And perhaps it will become one. Or perhaps we'll discover that some things are better left as nature intended, even when nature makes mistakes.
