CRISPR requires at least two basic components to alter genes: a guide RNA, which carries the code that specifies where to edit a genome, and an enzyme called Cas, which follows the guide RNA to make a cut in a cell’s DNA. Actually changing the DNA sequence, or inserting a new sequence, requires a third component—a DNA template—which has often led to lower rates of successful CRISPR editing. So instead of trying to fix the faulty DNA in sickle cell and β-thalassemia, Crispr Therapeutics is opting for a different approach to boost levels of healthy hemoglobin. Everyone is born with high levels of a protein called fetal hemoglobin, which is mostly replaced with adult hemoglobin by three months of age—the same time that symptoms of sickle cell and β-thalassemia appear. A gene called BCL11A represses fetal hemoglobin production, but a rare genetic mutation in this gene permits fetal hemoglobin production to continue, which effectively counteracts the effects of sickle cell and β-thalassemia mutations. Crispr Therapeutics’ lead drug candidate, CTX001, reproduces this mutation’s effect. It cuts BCL11A, “basically removing the brakes on fetal hemoglobin production,” Kulkarni says. The company recently presented results at a hematology meeting showing that its method edited over 90% of blood stem cells removed from patients with β-thalassemia, dramatically increasing fetal hemoglobin in these cells.
by Ryan Cross |
January 08, 2018