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Genetic editing: the first experiment was performed on a living patient to try to restore his sight.

Genetic editing: the first experiment was performed on a living patient to try to restore his sight.

today scientists have the ability to manipulate cells in previously unimaginable ways thanks to a peculiar technology called CRISPR.
From elegant studies that deciphered how CRISPR works in bacteria, researchers immediately discovered the biological potential of Cas9.

Eric Pierce's research, from Harvard Medical School, was first tested in a surgery performed by Mark Pennesi at the Oregon Health and Science University.

Within a month it will be known whether the genetic editing, first performed inside a patient's body, has had the expected results: nothing less than restoring sight to a person who was born with a hereditary form of blindness

This is an important step in manipulating DNA to treat diseases and conditions in humans.

The particularity of having done it inside the patient's body made this procedure innovative. It consisted in injecting the microscopic genetic editing tool, which uses the CRISPR technique, into the eye of the individual who volunteered. If in a few weeks it is verified that the approach can work, it will be necessary to wait another two or three months to see to what extent their vision is restored.

"We're helping to usher in, potentially, an era of genetic editing for therapeutic use that could impact many aspects of medicine," Eric Pierce, professor of ophthalmology at Harvard Medical School and director of the Retinal Disorders Service at the Massachusetts Eye and Ear Institute, told NPR. The intervention, which was conducted at Oregon Health & Science University, is part of a study Pierce is leading.

Until now, genetic editing has been done by taking cells out of the body to modify them in the laboratory and then infusing them back into the person.

The difference between this procedure and previous use of CRISPR in a few patients with cancer or rare blood disorders such as sickle cell anemia or beta-thalassemia is that doctors removed cells from the patients' bodies, edited them in the lab with the tool and then transfused the modified cells into the test volunteers, either to attack the cancer or to produce a protein that their bodies are missing. 

In this case the rewriting of the genetic code was done inside the eye of a person suffering from Leber's congenital amaurosis.

This rare genetic disease begins in childhood and progressively destroys the light-sensitive cells that the retina needs for vision. The degree of deterioration usually varies, but most patients are considered blind for legal purposes and can only distinguish light and dark or detect movement.

"Most people affected by this disease are at the more severe end of the spectrum in terms of their poor vision," Pierce told NPR. "Functionally, they are blind. We're really optimistic that this CRISPR gene editing directly in the patient can have a good chance of being effective.

The genetic code reprogramming was done in the eye of a patient with Leber congenital amaurosis, a rare genetic disease that causes vision loss. 

In a procedure lasting about an hour, doctors injected into the eyeball microscopic drops carrying billions of copies of a harmless virus that they had designed to carry instructions for building a CRISPR editing tool. 

This tool then cut out the genetic defect that causes blindness, in this case in the CEP290 gene. This could restore the production of a protein that is crucial for light-sensitive cells in the retina, and thus prevent them from dying. As other cells also recover, patients may be able to regain, even partially, their sight.

The total study of which this patient is a case involves 17 others patients affected by Leber's congenital amaurosis; among them, some are between three and 17 years old.

The Harvard researcher is conducting the study with Editas Medicine in Massachusetts and Allergan in Dublin, Ireland. Charles Albright, chief science officer of Editas, explained with Pierce that this first step is primarily to determine whether injecting the genetic editing tool into the eye is a safe procedure.

This is why we started with the lowest doses in older patients, who have already suffered enormous damage to their vision. And the doctors only treated one eye in each patient, Albright said. "These steps are taken in case the treatment somehow backfired and caused more damage, rather than helping. Because CRISPR has never been used directly inside a human body before, we want to make sure we do it right," Pierce said.

Francis Collins, director of the National Institutes of Health (NIH), called the breakthrough "a significant moment.

If the safety and effectiveness of the approach are confirmed, researchers will begin treating younger patients.
We believe that children have the potential to get the most benefit from their therapy because we know that their visual pathways of connection are still intact, Albright added.

Although there is no history of how long the results will last, the expectation is that if vision is restored by cutting out the gene mutation that causes vision loss, it will be a unique treatment for the rest of their lives.

But this case could go much further: "If we can do this safely, it opens up the possibility of treating many other diseases where it's not possible to take the cells out of the body to do the treatment outside," Pierce said.

For example, disorders that affect the brain such as Huntington's disease or inherited forms of dementia and muscle diseases such as muscular dystrophy or myotonic dystrophy, the researchers added.

Eric Pierce, of Harvard Medical School, is conducting this research with 18 volunteers from Editas Medicine and Allergan (Ocular Genomics Institute).

"We believe that the ability to edit within the body will open up whole new areas to medicine and lead to a whole new class of therapies for diseases that cannot be treated otherwise," Albright said. He was joined by Francis Collins, director of the National Institutes of Health (NIH), who called this breakthrough an important moment.

He told NPR, "We all dream that the day will come when we can apply this approach to thousands of diseases. This is the first time it's been used on a human being. And it gives us hope that we could extend this to many other diseases if it works and is safe.