A preliminary trial of a new way to use gene editing technology to fight disease produced exciting results. For the first time, researchers were able to show that it was safe and effective to use the CRISPR gene editing system directly inside patients’ bodies. This was a breakthrough because in previous CRISPR trials, patients’ cells had to be removed from their bodies, edited in the lab, and then infused back in. This new in-the-body technique, scientists believe, could have wide applications for treating a variety of genetic diseases.
In the trial, conducted by the companies Intellia Therapeutics and Regeneron, six people with a rare genetic disease called transthyretin amyloidosis were each given a single treatment of CRISPR therapy. All the study participants improved, and those who received the highest dosage improved the most.
Transthyretin amyloidosis is caused by a mutation in what is known as the TTR gene. Not everyone who has the mutation will get the disease, but those who do usually develop symptoms when they are adults. Symptoms get worse over time, and the disease is ultimately fatal.
The TTR mutation causes the liver to produce a misshapen protein that folds up the wrong way, clumps together, and damages various parts of the body, especially nerves and the heart. Because the disease is caused by the production of a single malformed protein, it was a great candidate for testing gene editing technology. If CRISPR therapy could stop the gene from directing the production of the badly formed protein, the progression of the disease could be stopped and maybe even reversed.
How CRISPR gene editing was used
The CRISPR system consists of two substances – an enzyme, called Cas9, that cuts the DNA, and a piece of RNA, called the guide, that carries the enzyme to the desired spot on the genome. In this trial, Cas9 snipped the DNA in the gene that produced the problematic protein. The cells’ natural healing processes took over to repair the cut, but there were often mistakes in the repair process. These mistakes disabled the gene and prevented it from making the bad protein.
One significant challenge that researchers faced was to keep the Cas9 and guide RNA from degrading inside the body before they could do their job. To solve the problem, the scientists encased the CRISPR system in lipids, which protected it. The liver took up the lipid-protected packages.
Results of the trial
Although the trial was small, involving only six test subjects, the results were highly encouraging. With only a single dose, the CRISPR gene editing treatment reduced the production of the misshapen protein in all of the test subjects.
One of the subjects had a 96% reduction. This surpassed the results that had been obtained using previous types of treatments for the disease, which had reduced the protein protection by 80% at most. The researchers were excited by the large reduction. They believed it could give the body a chance to clear out the harmful protein clumps that had accumulated because of the disease.
While researchers continue to conduct clinical trials with additional transthyretin amyloidosis patients and are eager to see how the patients fare over a longer time period, the results so far are highly encouraging. Being able to use CRISPR inside the body is expected to enable a broad range of applications to fight many genetic diseases. The technology for protecting the CRISPR system inside various parts of the human body is rapidly improving, which will pave the way for gene editing to be used for some of our most treatment-resistant diseases.
