The first person to have their genes edited inside their body wasn't treated in a gleaming research hospital in 2026. That milestone happened six years earlier, on March 4, 2020, when a surgeon at Oregon Health & Science University injected a solution containing molecular scissors directly into a patient's retina. The patient had been born with Leber Congenital Amaurosis type 10—a form of inherited blindness caused by a mutation too large for conventional gene therapy to fix. Now, with results from all 14 trial participants finally published, we know whether those scissors actually worked.

The Problem With CEP290

LCA10 stems from mutations in the CEP290 gene, which makes a protein essential for the light-sensing cells in your retina. Most patients with this condition are born blind or lose their vision in early childhood. The leading cause of inherited blindness in the first decade of life, it affects roughly 1 in 80,000 people.

For years, doctors had a theoretical solution: replace the broken gene with a working copy. That's how gene therapy typically works. You package a healthy gene into a harmless virus, inject it into the affected tissue, and let the virus deliver its genetic cargo. Simple enough.

Except CEP290 is enormous. At 2,500 base pairs, it's far too large to fit inside the adeno-associated viruses that serve as the delivery trucks for most gene therapies. These viral vectors have strict size limits—like trying to fit a couch through a car window. Traditional gene therapy simply couldn't reach this mutation.

How EDIT-101 Works

The BRILLIANCE trial took a different approach. Instead of replacing the entire gene, the treatment—called EDIT-101—uses CRISPR to perform genetic surgery. Think of it as the difference between replacing your entire hard drive versus deleting a corrupted file.

The specific mutation these researchers targeted, called IVS26, creates a defective section within the CEP290 gene. EDIT-101 delivers CRISPR's Cas9 enzyme (the molecular scissors) along with a guide RNA that directs those scissors to the exact location of the mutation. The enzyme cuts out the problematic DNA segment, leaving behind a shorter but functional gene.

The delivery happens through a single subretinal injection—a delicate surgical procedure that places the CRISPR components directly behind the retina in one eye. Because the edit happens in mature retinal cells that don't reproduce, the changes stay in the eye and aren't passed to future generations.

What Actually Happened to the Patients

Fourteen people received EDIT-101 between 2020 and the trial's completion: twelve adults aged 17 to 63, and two children aged 10 and 14. All were born with LCA caused by CEP290 mutations. Most couldn't read a single line on an eye chart before treatment.

The safety results, at least, were clean. No serious adverse events related to the treatment or procedure. No dose-limiting toxicity. For a first-in-human trial of a completely new approach—editing genes inside a living person's body—that alone qualified as a win.

The efficacy results, published in the New England Journal of Medicine in May 2024, showed something more interesting. Eleven of the fourteen participants—79%—demonstrated measurable improvements in at least one outcome measure. Four people gained clinically meaningful improvements in visual acuity. Six showed improvements in cone-mediated vision, which governs daytime and central vision.

The improvements weren't dramatic enough to restore normal sight. But for people who had lived their entire lives unable to see the food on their plates, being able to find a misplaced phone or notice the small indicator lights on a coffee machine represented genuine gains in independence.

The Gap Between Promise and Practice

These results tell a more nuanced story than either the triumphant headlines or the skeptical dismissals suggest. EDIT-101 worked—it was safe, it edited genes inside living human eyes, and most participants saw some benefit. But it didn't work spectacularly.

Part of the challenge involves timing. LCA10 causes damage from birth or early childhood. By the time patients entered this trial, many had already lost substantial numbers of photoreceptor cells. You can fix the genetic error, but you can't resurrect dead cells. The treatment might work better in younger patients with more intact retinas, which partially explains why the trial included two children.

The other challenge is one of measurement. The improvements patients reported—seeing food on plates, finding objects, noticing small lights—mattered immensely to their daily lives. But these gains didn't always translate into the standardized vision tests that regulatory agencies use to evaluate treatments. This gap between clinical measurements and lived experience complicates the path toward approval.

Beyond LCA10

As of late 2022, Editas Medicine was seeking a partner to advance EDIT-101 through further trials. The immediate future of this specific treatment remains uncertain. But the larger implications extend well beyond one rare form of blindness.

In vivo gene editing—editing genes inside the body rather than in cells removed and returned to the patient—opens possibilities for treating conditions that can't be addressed any other way. Diseases affecting the brain, the eye, the heart, or other organs where you can't simply extract cells, edit them in a lab, and put them back.

The eye served as an ideal testing ground: it's accessible, relatively isolated (reducing the risk that edited cells would spread), and small enough that you don't need massive doses of CRISPR components. Success here establishes proof of concept for editing genes in other solid organs.

Dr. Mark Pennesi, who led the OHSU arm of the trial, put it directly: being able to edit genes inside the human body is "incredibly profound." The fourteen participants in BRILLIANCE weren't just testing a treatment for their own condition. They were testing whether we can rewrite human genes in living tissue at all—whether the molecular scissors work as precisely in the complex environment of the human body as they do in a petri dish.

The answer appears to be yes, with caveats. The scissors cut where they're supposed to. The edits persist. The safety profile holds. What remains to be seen is whether we can sharpen those scissors enough to deliver not just measurable improvements, but transformative ones.