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Researchers used the gene-editing technique CRISPR within the human body for the first time, researchers said.

As part of the so-called the novel treatment was delivered through subretinal injection in a patient with Leber congenital amaurosis 10 (LCA10), a form of inherited blindness, said trial investigator Mark Pennisi, MD, PhD, of Oregon Health & Science University in Portland.

"It's very exciting because as an inherited retinal disease specialist, I see patients with diseases caused by over 300 different genes, and to date we've had very limited options for treating those patients," Pennisi told 名媛直播.

LCA10 is caused by a mutation of the CEP290 gene, inhibiting the production of light-making proteins that convert light into brain signals. It causes near or full blindness in children and there are currently no approved therapies to treat it.

A different gene therapy, voretigene neparvovec (Luxturna), was caused by mutations in the RPE65 gene.

Gene replacement therapy is also an option for some hereditary retinal diseases, but the viral vectors used for gene augmentation are too small for the genes that need to be targeted to treat LCA10, Pennisi said.

"Gene editing opens up the ability to treat genes that are larger than what we could do with gene replacement," he said.

Prior research has shown CRISPR to be safe, albeit not always effective, when genes edited outside of the body are transplanted back into patients. However, it was uncertain whether promising findings from the laboratory could be replicated in clinical studies.

The fact that gene-editing was performed within a live human is a "milestone moment for the gene-editing field" and especially for understanding the clinical potential of CRISPR enzymes, commented Satish K. Pillai, PhD, of the University of California San Francisco, who is not involved with the trial.

"We need to be cautious at this point because this is an experiment that's just been set in motion," Pillai told 名媛直播. "It's very exciting that they are testing this possibility, but as of now we don't really have any insights into whether this strategy will be effective or well-tolerated."

One concern is that the CRISPR-Cas9 technology will edit an off-site target, creating inadvertent mutations in other genes, Pillai said.

Compared to ex vivo gene editing, an in vivo procedure potentially carries a greater risk of having these off-target, deleterious effects, he added.

With this type of procedure, any off-site targeting would most likely take place in the retina itself, although there is a chance that the agent could circulate through the body and target other organs like the liver, said trial investigator Eric Pierce, MD, PhD, of Massachusetts Eye and Ear and Harvard Medical School in Boston.

"The risk of off-target activity like that is very low, but we can't say it's zero," Pierce told 名媛直播.

On the other hand, for some conditions, performing CRISPR gene-editing in vivo will be the only way to target diseased cells, Pillai said.

"For something like sickle cell disease, it's possible to do the editing on cells in the lab and then the corrected bone marrow can be reinfused," Pierce said. "We can't do that for other organs in the body and the retina is one of them because it's part of the central nervous system."

Altogether, 18 adult and pediatric participants are and the trial is expected to be completed by 2024.

"We're thrilled to be doing this because we could be helping open an era of therapeutic gene editing for many different disorders," Pierce said. "It feels momentous to me."

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