{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T19:23:28Z","timestamp":1776453808884,"version":"3.51.2"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>The development of genetic manipulation of <jats:italic>Plasmodium falciparum<\/jats:italic> in the 1980s was key to study malaria biology. Genetically modified parasites have been used to study several aspects of the disease, such as red blood cell invasion, drug resistance mechanisms, gametocyte development and mosquito transmission. However, biological and genetic differences between <jats:italic>P. falciparum<\/jats:italic> and the other human malaria parasites make <jats:italic>P.\u00a0falciparum<\/jats:italic> a poor model to study different species. The lack of robust systems of long-term <jats:italic>in vitro<\/jats:italic> culture of <jats:italic>P. vivax<\/jats:italic> and the other human malaria parasites lagged the genetic manipulation of these species. Here we review the efforts to generate genetically modified non-<jats:italic>falciparum<\/jats:italic> human malaria parasites, <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Using <jats:italic>in vivo<\/jats:italic> models \u2013 infection of non-human primates such as rhesus macaques and saimiri monkeys \u2013 researchers were able to generate transgenic lines of <jats:italic>P. knowlesi, P. cynomolgi<\/jats:italic>, and <jats:italic>P. vivax<\/jats:italic>. The development of long-term <jats:italic>in vitro<\/jats:italic> culture of <jats:italic>P. knowlesi<\/jats:italic> in the 2000\u2019s, using rhesus and human red blood cells, created a platform to genetically manipulate non-<jats:italic>falciparum<\/jats:italic> malaria parasites. Recently, the use of CRISPR\/Cas9 technology to genome edit <jats:italic>P. knowlesi<\/jats:italic> provides another tool to non-falciparum malaria research, extending the possibilities and allowing researchers to study different aspects of the biology of these parasites and understand the differences between these species and <jats:italic>P. falciparum<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fcimb.2021.680460","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T18:23:41Z","timestamp":1630693421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic Manipulation of Non-Falciparum Human Malaria Parasites"],"prefix":"10.3389","volume":"11","author":[{"given":"Ta\u00eds Baruel","family":"Vieira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thafne Plastina","family":"Astro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto Rudge de","family":"Moraes Barros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.ijpara.2018.02.004","article-title":"Infection of Mosquitoes From In Vitro Cultivated Plasmodium Knowlesi H Strain","volume":"48","author":"Armistead","year":"2018","journal-title":"Int. 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