Open AccessABO gene editing for the conversion of blood type A to universal type O in Rh null donor‐derived human‐induced pluripotent stem cells
Author(s) -
Petazzi Paolo,
MiquelSerra Laia,
Huertas Sergio,
González Cecilia,
Boto Neus,
MuñizDiaz Eduardo,
Menéndez Pablo,
Sevilla Ana,
Nogués Núria
Publication year - 2022
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.1063
Subject(s) - abo blood group system , induced pluripotent stem cell , crispr , human induced pluripotent stem cells , phenotype , red blood cell , medicine , biology , immunology , microbiology and biotechnology , genetics , gene , embryonic stem cell
The limited availability of red cells with extremely rare blood group phenotypes is one of the global challenges in transfusion medicine that has prompted the search for alternative self‐renewable pluripotent cell sources for the in vitro generation of red cells with rare blood group types. One such phenotype is the Rh null , which lacks all the Rh antigens on the red cell membrane and represents one of the rarest blood types in the world with only a few active blood donors available worldwide. Rh null red cells are critical for the transfusion of immunized patients carrying the same phenotype, besides its utility in the diagnosis of Rh alloimmunization when a high‐prevalence Rh specificity is suspected in a patient or a pregnant woman. In both scenarios, the potential use of human‐induced pluripotent stem cell (hiPSC)‐derived Rh null red cells is also dependent on ABO compatibility. Here, we present a CRISPR/Cas9‐mediated ABO gene edition strategy for the conversion of blood type A to universal type O, which we have applied to an Rh null donor‐derived hiPSC line, originally carrying blood group A. This work provides a paradigmatic example of an approach potentially applicable to other hiPSC lines derived from rare blood donors not carrying blood type O.