The pre-clinical data by Editas Medicine supports novel approach for treatment of sickle cell disease and beta-thalassemia.
Editas Medicine, Inc., a leading genome editing company, recently shared outcomes from experiments to demonstrate expanded CRISPR genome editing strategies in hematopoietic stem cells for the treatment of sickle cell disease and beta-thalassemia. In these experiments, the Cambridge, Massachusetts based organization demonstrated HBG1/2 promoter-edited CD34+ cells robustly engrafted in mice without lineage skewing of red blood cell precursors.
This data has been reported by the company in an oral presentation at the 60th Annual Meeting of the American Society of Hematology (ASH) in San Diego.
Insights of the experiments
In these experiments, NBSGW mice received an infusion of human CD34+ cells which had been edited either at the BCL11A erythroid enhancer (BCL11Ae) site or at the HBG1/2 promoter site. Analysis of bone marrow collected 8 to 16 weeks post-infusion demonstrated that robust fetal hemoglobin induction was achieved when targeting HBG1/2 promoters.
Notably, editing HBG1/2 promoters upregulated fetal hemoglobin with superior repopulation of red blood cell precursors as compared to editing the BCL11Ae site. The red blood cell precursors from bone marrow edited at the BCL11Ae site had lower productive editing rates compared to other lineages and showed an increased level of apoptosis, or programmed cell death, in erythroid culture compared to HBG1/2 promoter-edited cells.
Increased production of fetal hemoglobin can be beneficial to patients with sickle cell disease or beta-thalassemia. Reportedly, editing at the HBG1/2 site is a differentiated approach for development of a human therapeutic for the treatment of sickle cell disease and beta-thalassemia as compared to other medicines currently under development that edit at the BCL11Ae site.
The modern approach may give way to a safer and more effective medicine
Charles Albright, Ph.D., Chief Scientific Officer, Editas Medicine, stated, “We are encouraged by these preclinical results demonstrating cells edited at the HBG1/2 promoters repopulated all lineages of the blood system including, importantly, the red blood cell precursors. Editing at this site met our preclinical goals including robust, long-term induction of fetal hemoglobin and maintenance of normal hematopoietic stem/progenitor cell function.”
He added, “These findings further support our novel approach to developing a medicine for the potential treatment of sickle cell disease and beta-thalassemia. If these preclinical results translate to humans, we believe our editing approach for hemoglobinopathies may yield a safer and more effective medicine.”
About Editas Medicine
Founded in 2013, Editas Medicine focuses on translating the power and potential of the CRISPR/Cas9 and CRISPR/Cpf1 (also known as Cas12a) genome editing systems into a robust pipeline of treatments for people living with serious diseases around the world. As a leading genome editing company, it aims to discover, develop, manufacture, and commercialize transformative, durable, precision genomic medicines for a broad class of diseases.