CRISPR Therapeutics to launch first gene-editing clinical trial
Swiss genetic engineering firm CRISPR Therapeutics has sought permission from European regulators to begin its first-ever clinical trials early next year on CTX001, a gene therapy treatment for beta thalassemia. The company is also set to apply to the US Food and Drug Administration for approval to use it against sickle cell disease. CTX001 stimulates production of foetal haemoglobin, which the body usually cuts off at the age of around six months, and has resulted in an editing efficiency of 80%, with no reported off-target effects.

In late 2012, French microbiologist Emmanuelle Charpentier approached a handful of American scientists about starting a company, a Crispr company. They included UC Berkeley’s Jennifer Doudna, George Church at Harvard University, and his former postdoc Feng Zhang of the Broad Institute—the brightest stars in the then-tiny field of Crispr research. Back then barely 100 papers had been published on the little-known guided DNA-cutting system. It certainly hadn’t attracted any money. But Charpentier thought that was about to change, and to simplify the process of intellectual property, she suggested the scientists team up.

It was a noble idea. But it wasn’t to be. Over the next year, as the science got stronger and VCs came sniffing, any hope of unity withered up and washed away, carried on a billion-dollar tide of investment. In the end, Crispr’s leading luminaries formed three companies—Caribou Biosciences, Editas Medicine, and Crispr Therapeutics—to take what they had done in their labs and use it to cure human disease. For nearly five years the “big three’ Crispr biotechs have been promising precise gene therapy solutions to inherited genetic conditions. And now, one of them says it’s ready to test the idea on people.

Last week, Charpentier’s company, Crispr Therapeutics, announced it has asked regulators in Europe for permission to trial a cure for the disease beta thalassemia. The study, testing a genetic tweak to the stem cells that make red blood cells, could begin as soon as next year. The company also plans to file an investigational new drug application with the Food and Drug Administration to treat sickle cell disease in the US within the first few months of 2018. The company, which is co-located in Zug, Switzerland and Cambridge, Massachusetts, said the timing is just a matter of bandwidth, as they file the same data with regulators on two different continents.

Both diseases stem from mutations in a single gene (HBB) that provides instructions for making a protein called beta-globin, a subunit of hemoglobin that binds oxygen and delivers it to tissues throughout the body via red blood cells. One kind of mutation leads to poor production of hemoglobin; another creates abnormal beta-globin structures, causing red blood cells to distort into a crescent or “sickle” shape. Both can cause anemia, repeated infections, and waves of pain. Crispr Therapeutics has developed a way to hit them both with a single treatment.

It works not by targeting HBB, but by boosting expression of a different gene—one that makes fetal hemoglobin. Everyone is born with fetal hemoglobin; it’s how cells transport oxygen between mother and child in the womb. But by six months your body puts the brakes on making fetal hemoglobin and switches over to the adult form. All Crispr Therapeutics’ treatment does is take the brakes off.

From a blood draw, scientists separate out a patient’s hematopoietic stem cells—the ones that make red blood cells. Then, in a petri dish, they zap ‘em with a bit of electricity, allowing the Crispr components to go into the cells and turn on the fetal hemoglobin gene. To make room for the new, edited stem cells, doctors destroy the patient's existing bone marrow cells with radiation or high doses of chemo drugs. Within a week after infusion, the new cells find their way to their home in the bone marrow and start making red blood cells carrying fetal hemoglobin.