Information détaillée

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Titre du projet :

Transfusion Without Blood Typing: Enzymatic Glycoengineering Towards 'True' Universal Blood

Chercheur principal :

Kizhakkedathu, Jayachandran N; Withers, Stephen G

Co-chercheurs :

S/O

Directeur(s) de recherche :

S/O

Établisssement payé :

University of British Columbia

Établissement de recherche :

University of British Columbia

Département :

Pathology and Laboratory Medicine

Programme :

Subvention Projet

Concours (année/mois) :

202403

CEP désigné :

Génie biomédical 2

Institut principal :

Santé circulatoire et respiratoire

Thème principal :

Recherche biomédicale

Durée (année/mois) :

5 ans 0 mois

Contribution des IRSC :

Donateurs :

Montant :

1 013 626$

Équipement :

0$

Contribution du partenaire externe :

Nom du partenaire :

S/O

Montant :

S/O

Équipement :

S/O

Partenaire du candidat à l'externe :

Nom du partenaire :

S/O

Montant :

S/O

Équipement :

S/O

Partenaire externe (en nature) :

Nom du partenaire :

S/O

Montant :

S/O

Équipement :

S/O

Mots clés :

Blood Transfusion; Cell Surface Modification; Enzymatic Glycoengineering; Glycocalyx Extension; Glycosidases; Immune Matching; Immune Protection; Metagenomics; Polysialylation; Universal Blood

Résumé :

Blood transfusion is a valuable tool in modern medicine and is very important to the health of surgical patients, accident victims, sickle cell, thalassemia and cancer patients. In the current blood banking protocols, blood typing ensures the safety of patients as mismatched blood transfusion can be very dangerous. In emergency conditions, the knowledge of blood group of patients may not be available. Also, in certain group of patients who receive frequent blood transfusions (25 to 50 units/year) (e.g., thalassemia, sickle cell and myelodysplastic syndromes patients) develop mild to severe immune reactions due to mismatch of minor antigens (>370 on red blood cells (RBCs) which are of proteins or carbohydrates in nature) and are not usually typed. Finding matched blood is challenging to these group of patients. In this project, we are developing a novel glycoengineering approach to address this important unmet clinical need by creating 'true' universal blood. We are developing novel and specific enzymes (proteins) identified from human gut bacteria from donors to cleave A and B antigens on RBC surface specifically to generate O type blood cells. Further we are developing a novel an enzymatic extension of sugar coat that is naturally present on RBCs to mask the immunogenicity of minor antigens which are responsible of immune reactions in many patients. We will also combine these two approaches to generate 'true universal donor blood' which can be transfused to anyone thereby improving the safety and supply for diverse patients. We use the state-of-the-art enzyme discovery, engineering and cell surface modification together with studies in human blood and animal studies to prove the concept. The development of such technology will be a fundamental advance and improve health of many Canadians. We also foresee that this technology can used other cell therapies and generation of universal organs for transplantation.

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Version :

20250311.1