Cellectis Unveils a Non-Viral Gene Therapy Approach for Sickle Cell Disease in Nature Communications

Published on June 12, 2024

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New York, NY – June 12, 2024 – Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ:  CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, announced today the publication of a scientific article in Nature Communications, unveiling a non-viral gene therapy approach for sickle cell disease. 

Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. SCD is caused by a single point mutation in the HBB gene, which encodes the β subunit of hemoglobin (Hb). Normally, red blood cells adopt a disc-like shape that allows them to move easily through the blood vessels and deliver oxygen throughout the body. In sickle cell disease, red blood cells become crescent or “sickle”-shaped, a dysfunctional state that impairs blood flow, oxygen delivery and triggers multiple debilitating symptoms including intense pain crisis.  

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 (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 β-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. 

“The unique combination of TALEN® technology, non-viral DNA repair template design and Cellectis’ PulseAgile proprietary electroporation system enabled us to set up a precise, efficient and clinically relevant HBB gene correction process in long term hematopoietic stem and progenitor cells from SCD patients” said Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis. “SCD is a devastating blood disorder affecting millions of individuals worldwide. The TALEN® gene therapy approach could represent a new alternative treatment, especially for patients with limited therapeutic options. This gene editing process bears a strong therapeutic potential as it could be easily used to correct point mutations associated to many other genetic diseases.”  

Research data showed that: 

  • 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 (HbA) and a significant decrease of dysfunctional Sickle Hemoglobin (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.  

The article is available on Nature Communications website by clicking on this link: https://doi.org/10.1038/s41467-024-49353-3 

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