Pre-clinical

CRISPR crew’s lab test spotlights lead program in sickle cell disease, beta-thalassemia

Bill Lundberg, CSO, CRISPR

CRISPR/Cas9 tech is still at a very early stage of development. But one of the top biotechs looking to make a breakthrough in the clinic got a chance today to explain why one of its preclinical studies helps demonstrate gene editing’s promise in developing a radically new kind of therapy.

The company is CRISPR Therapeutics $CRSP and its preclinical program focuses on a different kind of approach in treating sickle cell disease as well as beta-thalassemia — two diseases triggered by a genetic mutation that slashes the natural production of hemoglobin.

Some people, though, have a genetic mutation that allows their bodies to continue to produce fetal hemoglobin. It’s a benign condition that is typically only found by chance. But creating this condition in these patients is a potential cure, and CRISPR Therapeutics made it their showcase program.

“Fetal hemoglobin can fully replace adult hemoglobin,” CRISPR Therapeutics CSO Bill Lundberg tells me. “There are some patients in whom that switch fails to turn off.”

Using its gene editing tech, investigators took CD34-positive progenitor cells from patient samples and created this condition in a therapeutic batch. Their abstract presented at the EHA meeting in Madrid on Friday concludes:

Using CRISPR/Cas9 we successfully created gene edits that upregulate HbF in both healthy donor and patient samples. We have also dissected the genotype-phenotype relationship for specific genetic modifications, identifying the editing strategies which are most promising for re-expressing HbF. We have optimized the conditions for modifying HSPCs, including at clinical scale in a GMP-compliant setting, and demonstrated potential safety with no detectable off-target editing. These experiments support the further development of specific CRISPR/Cas9 editing strategies of HSPCs to treat SCD and β-Thal patients.

“One of the great things about this program,” adds the CSO, “is that we know what effects it should lead to. We would look for that, look for fetal hemoglobin two to three months in, after patients receive it.”

It’s worth emphasizing again that this is a preclinical study and all such early lab experiments can at best just set the stage for what has to be tested in humans for an extensive period before any biotech can take a drug to regulators.

That is a long and risky journey at every stage, with plenty of twists expected along the way. And there are several rivals in the field, including Editas $EDIT and Intellia $NTLA. But for CRISPR Therapeutics, it also represents another goal post on the crucial lead-up to the clinic as they start to visualize getting to an application 3 or 4 or 5 years down the road.

Birthing any new technology isn’t easy. These kinds of potential revolutions never come cheap or easy, which is why it’s good for CRISPR Therapeutics to have $290 million in cash. But it will be studied at every step.


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