{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T10:23:25Z","timestamp":1793701405743,"version":"4.5.1"},"reference-count":69,"publisher":"American Society for Clinical Investigation","issue":"13","funder":[{"name":"National Institute of Health","award":["R01 AI125706"],"award-info":[{"award-number":["R01 AI125706"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,9]]},"abstract":"<jats:p>\n                    Whole-sporozoite vaccines engender sterilizing immunity against malaria in animal models and importantly, in humans. Gene editing allows for the removal of specific parasite genes, enabling generation of genetically attenuated parasite (GAP) strains for vaccination. Using rodent malaria parasites, we have previously shown that late liver stage\u2013arresting replication-competent (LARC) GAPs confer superior protection when compared with early liver stage\u2013arresting replication-deficient GAPs and radiation-attenuated sporozoites. However, generating a LARC GAP in the human malaria parasite\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    (\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    ) has been challenging. Here, we report the generation and characterization of a likely unprecedented\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    LARC GAP generated by targeted gene deletion of the\n                    <jats:italic>Mei2<\/jats:italic>\n                    gene:\n                    <jats:italic>\n                      P. falciparum mei2\n                      <jats:sup>\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    . Robust exoerythrocytic schizogony with extensive cell growth and DNA replication was observed for\n                    <jats:italic>\n                      P. falciparum mei2\n                      <jats:sup>\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    liver stages in human liver-chimeric mice. However,\n                    <jats:italic>\n                      P. falciparum mei2\n                      <jats:sup>\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    liver stages failed to complete development and did not form infectious exoerythrocytic merozoites, thereby preventing their transition to asexual blood stage infection. Therefore,\n                    <jats:italic>\n                      P. falciparum mei2\n                      <jats:sup>\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    is a replication-competent, attenuated human malaria parasite strain with potentially increased potency, useful for vaccination to protect against\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    malaria infection.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.135589","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T12:02:17Z","timestamp":1591099337000},"source":"Crossref","is-referenced-by-count":76,"title":["A replication-competent late liver stage\u2013attenuated human malaria parasite"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5878-0482","authenticated-orcid":true,"given":"Debashree","family":"Goswami","sequence":"first","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Betz","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navin K.","family":"Locham","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0998-7764","authenticated-orcid":true,"given":"Chaitra","family":"Parthiban","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Brager","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Camargo","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thao","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7262-1055","authenticated-orcid":true,"given":"Spencer Y.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-0131","authenticated-orcid":true,"given":"Sean C.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley M.","family":"Vaughan","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, Washington, USA."},{"name":"Department of Pediatrics, University of Washington, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H.I.","family":"Kappe","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, Washington, USA."},{"name":"Department of Pediatrics, University of Washington, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"B1","unstructured":"World Health Organization. World Malaria Report 2019. World Health Organization website. https:\/\/www.who.int\/publications-detail\/world-malaria-report-2019 Published December 4, 2019. Accessed June 4, 2020"},{"issue":"8","key":"B2","doi-asserted-by":"crossref","DOI":"10.1111\/pim.12628","article-title":"Immune effector mechanisms in malaria: an update focusing on human immunity","volume":"41","author":"Moormann","year":"2019","journal-title":"Parasite Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)80069-7"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120220"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.09.098"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00025-08"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.17-0343"},{"key":"B8","unstructured":"European Medicines Agency. First malaria vaccine receives positive scientific opinion from EMA. 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