CRISPR-Cas9 Used to Remove RBC Antigens to Improve Success of Blood Transfusions

CRISPR-Cas9 Used to Remove RBC Antigens to Improve Success of Blood Transfusions

Blood transfusions are necessary for the treatment of diseases such as thalassaemia or sickle-cell disease. The blood donation service generally meets patients’ needs, although for some patients with rare blood groups it can be difficult to find sufficient numbers of donors.

Blood can be matched with patients using the major blood group antigens, but red blood cell surface antigens are complex. There are more than 350 different antigens present on red blood cells that are recognized by the International Society of Blood Transfusion. Any mismatch, even with minor blood group antigens, can result in alloimmunisation. Typically, this occurs in around 2-5% of blood transfusions.

However, alloimmunisation occurs in around 30% of patients who require multiple blood transfusions, such as chronically transfused sickle‐cell disease patients. That increases the difficulty in finding suitable donors further still. Patients with particularly rare blood group phenotypes such as the Bombay phenotype reduces the number of potential donors further still. Just one in a million patients have that phenotype in Europe.

One potential solution is to culture red blood cells in the lab. Significant advances have been made in this area in recent years with blood cells having been cultured from embryonic and pluripotent stem cells. If donor cells can be obtained from individuals with rare blood types, it would be possible to generate rare blood cells in vitro.

An alternative would be to use genetic engineering techniques to improve compatibility of blood cells grown in vitro, and a significant advance has been made in this area by researchers at the NIHR Blood and Transplant Research Unit, BrisSynBio Center, and Bristol’s NHS Blood and Transplant unit. The team has use CRISPR-Cas9 to create cell lines that can be differentiated into functional reticulocytes completely deficient in transfusion‐relevant blood groups.

“We use CRISPR-mediated genome editing of an immortalised human erythroblast cell line (BEL-A) to generate multiple enucleation competent cell lines deficient in individual blood groups,” wrote the authors of the paper. “Edits are combined to generate a single cell line deficient in multiple antigens responsible for the most common transfusion incompatibilities: ABO (Bombay phenotype), Rh (Rhnull), Kell (K0), Duffy (Duffynull), GPB (S−s−U−).”

While there are many hurdles to overcome, it is hoped that this technique could one day be used to provide compatible transfusions for patients with rare blood phenotypes for whom matching is particularly difficult or impossible.

The paper – Enhancement of Red Blood Cell Transfusion Compatibility Using CRISPR-Mediated Erythroblast Gene Editing – was recently published in the journal EMBO Molecular Medicine.

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