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A recent clinical trial with a WSp vaccine comprising genetically attenuated parasites (GAP) which arrest growth early in the liver (PfSPZ-GA1), showed that GAPs can be safely administered to humans and immunogenicity is comparable to radiation-attenuated PfSPZ Vaccine. GAPs that arrest late in the liver stage (LA-GAP) have potential for increased potency as shown in rodent malaria models. Here we describe the generation of four putative <jats:italic>P. falciparum<\/jats:italic> LA-GAPs, generated by CRISPR\/Cas9-mediated gene deletion. One out of four gene-deletion mutants produced sporozoites in sufficient numbers for further preclinical evaluation. This mutant, <jats:italic>Pf<\/jats:italic>\u0394<jats:italic>mei2<\/jats:italic>, lacking the <jats:italic>mei2-like RNA<\/jats:italic> gene, showed late liver growth arrest in human liver-chimeric mice with human erythrocytes, absence of unwanted genetic alterations and sensitivity to antimalarial drugs. These features of <jats:italic>Pf<\/jats:italic>\u0394<jats:italic>mei2<\/jats:italic> make it a promising vaccine candidate, supporting further clinical evaluation. <jats:italic>Pf<\/jats:italic>\u0394<jats:italic>mei2<\/jats:italic> (GA2) has passed regulatory approval for safety and efficacy testing in humans based on the findings reported in this study.<\/jats:p>","DOI":"10.1038\/s41541-022-00558-x","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T17:04:58Z","timestamp":1667581498000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-4182","authenticated-orcid":false,"given":"Blandine","family":"Franke-Fayard","sequence":"first","affiliation":[]},{"given":"Catherin","family":"Marin-Mogollon","sequence":"additional","affiliation":[]},{"given":"Fiona J. 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