Gene editing to improve red cell transfusion compatibility

Synthetic biologists at the University of Bristol have succeeded in generating laboratory-made red blood cells with rare blood group types that could one day be used to help patients who cannot be matched with donor blood.

The provision of blood for patients who require repeated blood transfusions, as well as for individuals with rare blood types, presents an enormous challenge to transfusion services worldwide. While most people can safely receive a blood transfusion from donated blood, patients with blood disorders such as thalassaemia or sickle cell disease require frequent transfusions. With repeated transfusion, patients eventually develop an immune response to all but the most specifically matched donor blood, due to incompatibility at the level of minor blood group antigens.

Using CRISPR-Cas9-mediated gene editing, the team based at the NIHR Blood and Transplant Research Unit (NIHR BTRU), BrisSynBio Centre and NHS Blood and Transplant in Bristol created individual cell lines in which specific blood group genes were altered to prevent the expression of blood group proteins that can cause immune reactions.

Building on this gene-editing approach, the team then went on to produce cells that combined the deletion of multiple blood groups in a single cell line that could be differentiated to generate functional novel red blood cells with extremely broad transfusion compatibility. Transfusions of red blood cells edited to improve compatibility could provide better treatments for those patients whose clinical needs are difficult to meet.

This study, published in the EMBO Molecular Medicine journal, provides the first proof-of-principle demonstration that gene editing can be used in combination with laboratory culture of red blood cells to generate rare or customised red blood cells for patients with specific needs.

http://embomolmed.embopress.org/cgi/doi/10.15252/emmm.201708454

 

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