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Through a combination of RNA interference screening in erythroid cells and validation by CRISPR\/Cas9\u2010mediated knockout in primary human hematopoietic stem cells, we identified the glycosyltransferase Core 1 Synthase Glycoprotein\u2010N\u2010Acetylgalactosamine 3\u2010Beta\u2010Galactosyltransferase 1 (C1GALT1) as a novel host determinant for\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    invasion. Analyses of C1GALT1\u2010deficient cultured reticulocytes and RBCs with the glycophorin A\/B\u2010null M\n                    <jats:sub>k<\/jats:sub>\n                    M\n                    <jats:sub>k<\/jats:sub>\n                    blood group phenotype demonstrated that the C1GALT1\u2010dependent \u03b1(2\u20103) sialic acid structures within mucin\u2010type O\u2010glycans are crucial for efficient invasion of both sialic acid\u2010dependent and sialic acid\u2010independent\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    strains, but not the primate malaria parasite\n                    <jats:italic>Plasmodium knowlesi<\/jats:italic>\n                    . However, different\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    parasite strains exhibit variable dependencies on distinct sialic acid configurations on the RBC surface. Overall, our findings highlight a key role for RBC glycans in malaria infection.\n                  <\/jats:p>","DOI":"10.1002\/ajh.70037","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T06:32:03Z","timestamp":1756535523000},"page":"1952-1962","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sialyl\u2010T Antigen: A Novel Red Blood Cell Determinant for\n                    <i>Plasmodium falciparum<\/i>\n                    Invasion"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3449-2851","authenticated-orcid":false,"given":"Mahmoud","family":"Mikdar","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Diseases Harvard T. H. 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