On December 11, 2017 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on the development of potentially curative therapeutics using the CRISPR technology, and its collaborator, Novartis, reported initial data from their research collaboration on genome-edited human hematopoietic stem cells (Press release, Intellia Therapeutics, DEC 11, 2017, View Source [SID1234522514]). These data showed successful ex vivo editing of the erythroid specific enhancer of BCL11A, a gene associated with prevention of sickle cell disease, and the ability of these cells to stably engraft in mice while maintaining their desired properties.
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These data were presented today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in the platform presentation session: Hemoglobinopathies, Excluding Thalassemia – Basic and Translational Science: Sickle Cell Disease – Hematopoiesis and Fetal Hemoglobin Augmentation. In the presented studies, the companies:
Achieved approximately 80-95 percent target site modification in human hematopoietic stem and progenitor CD34+ cells following electroporation of ribonucleoprotein (RNP) composed of Cas9 and a guide RNA (gRNA), selected for efficacy and potency;
Demonstrated an approximately 40 percent reduction in BCL11A mRNA with a corresponding two-fold increase in γ-globin transcript and 30-40 percent more fetal hemoglobin-positive cells above background. Similar decreases in BCL11A mRNA and increases in γ-globin transcipt were observed when sickle cell disease-derived cells from patient donors were edited;
Achieved engraftment over 16 weeks following transplantation of edited human bone marrow CD34+ cells into immune compromised mice, while maintaining editing levels in engrafted cells; and
Observed no off-target events in CD34+ cells edited with the selected gRNA, as measured by targeted next generation sequencing of sites identified through in silico prediction and based on an unbiased, genome-wide, oligo-insertion detection method.
"We are pleased to be reporting data from studies generated through Intellia’s collaboration with Novartis, demonstrating successful ex vivo CRISPR/Cas9 editing in hematopoietic stem cells," said John Leonard, M.D., executive vice president, Research & Development, Intellia Therapeutics. "These results are significant as we have shown high levels of editing as well as increased production of fetal hemoglobin to clinically relevant levels, which could potentially ameliorate sickle cell disease in affected patients. We are very encouraged to present this progress given that sickle cell disease is a serious condition that currently has limited treatment options."
About Sickle Cell Disease
Sickle cell disease is a life-threatening, hereditary disorder that impacts approximately 30 million people worldwide. The disease results from a single amino acid change in the β-globin gene, which causes polymerization of hemoglobin and the deformation of red blood cells, leading to vaso-occlusion, severe pain crisis and multi-organ dysfunction. The average life expectancy in the developed world is 40 to 60 years. About 80 percent of sickle cell disease cases are believed to occur in sub-Saharan Africa.