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Scientists Are Using CRISPR in Attempts to Restore Vision, Cure Blood Disorders, and More

New clinical trials are underway to treat human patients with CRISPR, a technique that edits DNA in cells

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TThe vast majority of existing medicines only treat symptoms of disease, rather than the root cause of them. But gene-editing technology, which allows scientists to tweak DNA, could lead to outright cures in the not-so-distant future.

At least that’s the promise of CRISPR, a powerful gene-editing tool that could revolutionize medicine. In 2013, scientists published the first study using CRISPR to cut and paste DNA in living human cells in a lab. Now, biotech companies are putting that idea to the test in human patients. A handful of clinical trials using CRISPR are in progress in the United States, Europe, and China.

Likened to molecular scissors, CRISPR’s power lays in its ability to snip out errant bits of genetic code, or replace genes altogether. In the first clinical trials, scientists will attempt the former. Swapping out nonworking genes for new ones is a more complicated undertaking, one that will likely take a few more years of lab and animal testing before it’s tried in people.

Companies have been eager to commercialize CRISPR, with a slew of startups springing up over the past six years, including CRISPR Therapeutics, Editas Medicine, and Intellia Therapeutics. But despite the fervor around CRISPR, these initial human studies demonstrate the abundance of caution with which these companies are approaching gene editing in human beings. They’ll start out treating small numbers of patients. And CRISPR will only be used in the eye, or on cells outside the body at first. That’s to make sure the treatments are safe and won’t wreak havoc on other parts of the genome.

Restoring vision

Genome-editing company Editas Medicine, and pharma partner Allergan, announced in July that they will soon test CRISPR on patients with an inherited form of blindness, called Leber congenital amaurosis 10. People born with this condition have severe vision loss that starts in early childhood, and some of them go completely blind. A mutation in the CEP290 gene causes their photoreceptors — the light-sensing cells that make vision possible — to deteriorate over time.

Editas’ experimental treatment uses CRISPR to snip out the mutation in the CEP290 gene. The therapy will be injected directly into the eye behind the retina. The company thinks this approach will repair the remaining photoreceptors and restore vision.

The trial will be the first so-called in vivo use of CRISPR in humans — meaning the therapy will be injected directly into the body. In a company press release, Ben Yerxa, CEO of the Foundation Fighting Blindness, called it a “potentially life-changing medicine.”

The eye is a good starting point, since it demands a very small dose. There’s also little risk of the therapy traveling anywhere else in the body. That’s important, because one of the clearest risks of CRISPR is that it could inadvertently make edits in a part of the genome it’s not supposed to — what are known as off-target effects.

Editas had planned to seek permission from the U.S. Food and Drug Administration in 2017 to move ahead with human testing but didn’t do so until 2018. The company cited manufacturing issues as the reason for the delay. Now, the highly anticipated trial is finally getting underway. Editas and Allergan say they are enrolling 18 patients from age three to adulthood in the initial trial.

CRISPR will only be used in the eye, or on cells outside the body at first. That’s to make sure the treatments are safe and won’t wreak havoc on other parts of the genome.

Curing blood disorders

While the Editas therapy will attempt to directly edit cells in the body, another company is editing cells outside the body in a lab, then putting the modified cells back into patients in hopes of effectively curing them.

CRISPR Therapeutics, which has partnered with Vertex Pharmaceuticals, kicked off its first human trial in Germany last August. This trial aims to treat a blood disorder called beta thalassemia. Earlier this year, the company began another trial in the United States to treat sickle cell disease, a related blood disorder. So far, the company has treated one patient in Germany and one in the United States. About 15,000 people in Europe have beta thalassemia, and an estimated 100,000 in the United States — most of them African American — have sickle cell.

Beta thalassemia patients rely on regular blood transfusions that can be as frequent as every two weeks. In a July press release, the company says the beta thalassemia patient in Germany hasn’t needed a blood transfusion in the four months since the treatment.

Both diseases can be life-threatening, and both are caused by errors in the gene that makes hemoglobin, a crucial protein in red blood cells that carries oxygen throughout the body. Typically, a person needs to inherit two copies of the mutated gene — one from mom and one from dad — to have symptoms. In beta thalassemia, the body doesn’t make enough hemoglobin. In sickle cell disease, the body makes an abnormal form of hemoglobin that gives red blood cells a sickled shape. These sickled cells stick together and clog blood vessels, which blocks oxygen flow and causes pain episodes.

CRISPR Therapeutics is attempting to treat both diseases in the same way. Everyone is born with a fetal hemoglobin gene that gets shut off after birth. In both clinical trials, scientists are using CRISPR to delete a piece of genetic code, which will turn that fetal gene back on in a person’s blood stem cells. The company’s therapy is similar to a bone marrow transplant — which replaces unhealthy blood stem cells with healthy ones from a donor — with an extra step added. And instead of using stem cells collected from a donor’s bone marrow, scientists at the company are extracting stem cells from a patient’s own bone marrow. They will then edit them with CRISPR in a lab and transplant the modified cells back into the patient. The idea is that the edited stem cells will travel back to the bone marrow, where they will begin to make healthy red blood cells.

“Our goal is to provide patients with a potentially curative treatment option — a dramatic reduction or elimination of symptoms,” says Samarth Kulkarni, CEO of CRISPR Therapeutics. “This could be a one-and-done, but it’s still early days.”

Scientists think this approach will help minimize any potential risks of CRISPR. By editing cells outside the body, they can observe whether the edits were effective before reintroducing those cells into patients.

The sickle cell study is recruiting patients in New York, Philadelphia, Houston, Nashville, and Memphis, as well as in Canada, Germany, and Italy.

The vision trial will be the first so-called in vivo use of CRISPR in humans — meaning the therapy will be injected directly into the body.

Supercharging T cells against cancer

Philadelphia-based startup Tmunity is testing a CRISPR therapy for certain types of cancer that have recurred. The company is conducting a clinical trial at the University of Pennsylvania. In May, the first two patients — one with multiple myeloma, a type of blood cancer, and one with sarcoma, which occurs in the bones and connective tissues — received the Tmunity therapy. No further patients have been treated yet, though there are expected to be up to 18 participants in the trial. The company has yet to provide an update on the conditions of the treated patients.

Tmunity’s approach also uses CRISPR to edit cells outside the body. In this case, scientists are drawing blood from patients and extracting T cells — a type of immune cell — from the samples. They then use CRISPR to remove two genes from the T cells and turn on a third one, essentially supercharging them against cancer. The cells will then be infused back into the patients.

The procedure is similar to CAR T-cell therapy, which involves modifying a patient’s T cells in the lab so that they will attack cancer cells. Two CAR T-cell therapies, Kymriah and Yescarta, are already approved by the FDA, but neither uses CRISPR to modify patients’ T cells.

Tmunity was spun out of Penn by star scientists Carl June and Bruce Levine, who have pioneered CAR T-cell therapy. The Parker Institute for Cancer Immunotherapy, founded by tech billionaire Sean Parker in 2016, is also funding the study. The trial took more than two years to get off the ground while it addressed concerns posed by the FDA.

CRISPR Therapeutics is also beginning a trial to use the gene-editing tool to treat certain types of cancer. In China, at least a half-dozen trials using CRISPR for cancer are starting or ongoing.

As promising as the CRISPR trials are, it will likely be months or years before we know for sure whether any of these therapies are effective and long-lasting. And before CRISPR can be used more broadly in medicine, scientists will need to do a lot more testing to make sure the gene-editing tool is truly safe.

Former staff writer at Medium, where I covered biotech, genetics, and Covid-19 for OneZero, Future Human, Elemental, and the Coronavirus Blog.

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