Cellectis publishes approach for sickle cell disease in Nature Communications

Cellectis announced the publication of a scientific article in Nature Communications, unveiling a non-viral gene therapy approach for sickle cell disease. Cellectis leverages Talen technology and a non-viral gene repair template delivery to develop a clinically relevant gene editing process in hematopoietic stem and progenitor cells, or HSPCs. This process enables efficient HBB gene correction with high precision, specificity and minimal genomic adverse events. Applying this HBB gene correction process to SCD patient-HSPCs results in over 50% expression of normal adult hemoglobin in mature red blood cells and in the correction of sickle phenotype, without inducing ss-thalassemic phenotype. Edited HSPCs engraft efficiently in an immunodeficient murine model and maintain clinically relevant levels of HBB gene correction events. This comprehensive preclinical data package sets the stage for the therapeutic application of autologous gene corrected HSPCs to address SCD. Talen technology, coupled to non-viral DNA correction template delivery, achieves high HBB gene correction efficiencies in healthy donor – and SCD patient – HSPCs in vitro. HBB gene correction translates into an efficient rescue of functional Adult Hemoglobin, or HbA, and a significant decrease of dysfunctional Sickle Hemoglobin, or HbS, and Sickle red blood cells. Talen nuclease activity is highly specific with only one off-target site detected at the HBD locus. Corrected HSPCs display long-term in vivo engraftment capacity in murine animal model, indicating their strong potential for therapeutic applications towards SCD.