Early Study Shows Promise of CRISPR Injection to Treat Rare Disease

Three people who received a high dose of the gene editing tool in a clinical study saw significant improvement in their condition

CRISPR allows scientists to cut and insert small slices of DNA with precision, illustrated here.
CRISPR allows scientists to cut and insert small slices of DNA with precision, illustrated here.

A study published on June 26 in the New England Journal of Medicine presents the first evidence that the gene editing tool CRISPR can be used to treat a rare disease by injecting it into a person’s bloodstream, Jocelyn Kaiser reports for Science magazine.

The researchers worked with six volunteers with transthyretin amyloidosis, a disease caused by one malfunctioning gene that results in pain, numbness and heart disease. Although the disease can arise randomly, the six volunteers had inherited the condition from their parents. Three of the volunteers received a high dose of the CRISPR-based treatment, and data gathered after four weeks shows that the treatment performs as well as, or better than, the current standard treatment for amyloidosis.

"It really is exciting," says Julian Gillmore, who specializes in amyloidosis and ran the study at University College London’s Royal Free Hospital, to Rob Stein at NPR. "This has the potential to completely revolutionize the outcome for these patients who have lived with this disease in their family for many generations. It's decimated some families that I've been looking after. So this is amazing.”

The treatment developed for the study, which was sponsored by Intellia and Regeneron, delivers the genetic code for CRISPR, written in messenger RNA, to the liver along with a second, guide RNA, by wrapping them both in oily capsules called nanoparticles.

When the nanoparticles reach the liver, they release the messenger RNA and guide RNA. Cells in the liver use the messenger RNA to create the CRISPR gene editing protein, and the guide RNA leads that protein to the DNA of the gene that causes amyloidosis. There, the protein cuts the DNA. The cell quickly repairs the damage, but imperfectly, which stops the cell from reading the disease-causing gene in the future.

Four weeks after the treatment, three of the participants who received a higher dose of nanoparticles had an 80 to 96 percent drop in levels of the disease-causing toxin produced by that gene. If the technique is successful in further trials, it could offer a one-time treatment for amyloidosis—an improvement over the current standard treatment, which provides temporary relief and must be injected regularly.

“These are stunning results,” says University of Pennsylvania cardiologist Kiran Musunuru, who was not involved in the study, to Science magazine. “It exceeds all my expectations.”

For Patrick Doherty, a participant in the study, amyloidosis symptoms first appeared as a pins-and-needles feeling in his fingers and toes, he tells NPR. Then his feet became cold, and he noticed he was becoming out of breath after walking uphill despite being a hiker. But his father had also been affected by the disease.

"It's terrible prognosis. This is a condition that deteriorates very rapidly. It's just dreadful," says Doherty to NPR. So when he learned he could volunteer for the study, "I thought: Fantastic. I jumped at the opportunity.”

The initial study’s results are promising. Now the researchers are planning further trials with more patients and longer follow-up times, using the higher dose from the initial study, in order to be sure that the treatment is safe and effective, per a statement by Intellia.

The findings also suggest that CRISPR could be more widely useful as a tool to treat other diseases.

"While these are early data, they show us that we can overcome one of the biggest challenges with applying CRISPR clinically so far, which is being able to deliver it systemically and get it to the right place," says University of California, Berkeley, biochemist Jennifer Doudna, whose work developing CRISPR earned her a share of the Nobel Prize in 2020. "This is a major milestone for patients.”