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A new gene-editing technique could help treat sickle cell anemia

Scientists hope to have a clinical trial in the next five years

Blood Bags

A new treatment for the blood disease sickle cell anemia is possible now that scientists have figured out how to repair the mutation that causes the condition. It doesn’t work all the time, but it does create hope for patients.

Researchers took blood from patients from sickle cell anemia. Then, they used a gene-editing technique called CRISPR to snip out the genetic mutation and replace it with healthy DNA, as described in a study published today in Science Translational Medicine. The procedure is very difficult, so only 6 percent of the cells, at most, were fully fixed. This is far from ideal, but 6 percent is theoretically still enough to help patients. The blood didn’t go back in the patients, so we don’t know what its effects on their condition might be. But the hope is that we can one day treat patients by giving them transfusions of their own, fixed blood, says study co-author Dana Carroll, a professor of biochemistry at the University of Utah.

Sickle cell anemia is caused by a single gene mutation that makes the body produce red blood cells in a “sickle” shape, instead of the regular one, which looks kind of like a jelly donut with a dent in the middle. These unhealthy blood cells can lead to pain and weakness and damage the organs. A type of bone marrow transplant can treat the disease. First, the patient’s immune system is suppressed. Then, stem blood cells found in the marrow are destroyed and replaced with healthy cells from a donor. But sometimes the body rejects the donor cells; because of this, transfusions aren’t used very often, especially for children. But if patients receive their own healthy cells, one big problem will be solved and the treatment can help more people.

To fix the mutation, the team created a special pre-formed molecule that works like using a pair of scissors to snip directly at the gene. Other methods, without the pre-formed molecule, are like sending scissor parts to the tailor and asking them to put the scissors together before snipping. The procedure is “technically well-done and kind of a tour de force” says Krishanu Saha, a professor of bioengineering at the University of Wisconsin-Madison who was not involved with the study.

This isn’t the first time people have tried to fix the sickle gene mutation. Earlier, scientists figured out how to edit out the mutation in normal blood cells, but they failed when it came to stem cells. (We’re not exactly sure why this is.) Problem is, normal blood cells eventually vanish, but the stem blood cells last and create more blood cells, so the benefits would last much longer. “We thought that by using the CRISPR system and a new method of delivery, that maybe we could do better than that,” says Carroll.

They were right: they could edit stem cells, too. When the researchers gave mice the fixed blood, the stem cells lasted for four months. Carroll says that these stem cells could theoretically last for life in humans. The promise isn’t just for sickle cell, either — it could potentially help with other blood diseases, too.

This method is more successful than anything we’ve seen before, but there’s still room for improvement. Fixing the mutation is a two-step process: first, disabling the genome, and then actually repairing the part that was mutated so it works properly. The team disabled the gene about half of the time, but they were only able to repair it up to 6 percent of the time, according to Carroll. So in the end the blood transfusion was made up of 6 percent corrected cells, 50 percent disabled cells. The remaining half still had the mutation.

This success rate is just good enough to be potentially helpful. Previous research in sickle cell anemia shows that even if only about 5 percent of the cells are “healthy,” the patient can still get better.

Researchers have focused on sickle cell anemia in part because it’s caused by a mutation in a single place, which makes “solving” it a lot more simple than with a disease caused by many different mutations. It’s also very common; just in the US, it affects 90,000 people, mostly African-Americans. The next steps are to improve the technique’s success rate — and, perhaps, to start a clinical trial in the next five years.