CRISPR Used to Treat Rare Genetic Disease for First Time

In March of last year doctors in Oregon used CRISPR inside a person’s body for the first time. Now, another team of doctors, this time in England, has used the revolutionary gene editing tool in vivo once again. This time for a trial attempting to treat people with a rare genetic disorder that causes the buildup of a harmful protein in their organs.

NIH

Science magazine reported on the new trial led by professor of medicine Julian Gillmore of University College London. Gillmore and her colleagues performed their trial at the Royal Free Hospital in England’s capital city, attempting to treat six patients for the rare genetic disease known as hereditary transthyretin amyloidosis (or TTR).

To treat the six patients, Gillmore’s team used a combination of CRISPR and mRNA technology. In essence, delivering the “clustered regularly interspaced short palindromic repeats”—a family of DNA sequences found in the genomes of bacteria—via the same kind of lipid particles, or fat bubbles, that deliver the genetic codes for the spike proteins the COVID-19 vaccines use.

UC Berkeley / Roxanne Makasdjian et al. 

The doctors used the DNA sequences inside of fat bubbles to target mutated genes inside the patients’ liver cells. The malfunctioning genes churn out “misfolded” forms of the protein, transthyretin, which builds up on nerves and the heart; in turn leading to pain, numbness, and heart disease.

Delivering the genetic code for the protein Cas— the CRISPR sequence that snips DNA, in the visualization above—via the lipid bubbles, the doctors were able to delete the liver cells’ malfunctioning genes. And, most notably, significantly reduced the amount of transthyretin in participants’ bodies. By up to 96% in one case, and, on average, more than 50%.

“This is wonderful news for patients with this condition,” Gillmore said in a press release. “If this trial continues to be successful, the treatment may permit patients who are diagnosed early in the course of the disease to lead completely normal lives without the need for ongoing therapy,” the professor added.

As for downsides, the doctors only report “mild adverse events” amongst trial participants. Although six people, of course, is a very small trial. Regardless, it seems that many doctors and scientists not involved with the trial are encouraged by its results. Jennifer Doudna of the University of California Berkeley, who shared a Nobel Prize last year for discovering CRISPR, for example, told Science that this work is “a critical first step in being able to inactivate, repair, or replace any gene that causes disease” anywhere in the body. Which, frankly, sounds like it’s plausible, but still a very long way off.