Abstract
The development of genetic manipulation of Plasmodium falciparum 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 P. falciparum and the other human malaria parasites make P. falciparum a poor model to study different species. The lack of robust systems of long-term in vitro culture of P. vivax and the other human malaria parasites lagged the genetic manipulation of these species. Here we review the efforts to generate genetically modified non-falciparum human malaria parasites, in vivo and in vitro. Using in vivo models – infection of non-human primates such as rhesus macaques and saimiri monkeys – researchers were able to generate transgenic lines of P. knowlesi, P. cynomolgi, and P. vivax. The development of long-term in vitro culture of P. knowlesi in the 2000’s, using rhesus and human red blood cells, created a platform to genetically manipulate non-falciparum malaria parasites. Recently, the use of CRISPR/Cas9 technology to genome edit P. knowlesi 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 P. falciparum.
Highlights
Bacterial transformation was discovered in 1955 (Hotchkiss, 1955) and since scientists have been able to manipulate the genomes of several organisms using the same principle
In this paper we review all the published papers on genetic transformation of non-falciparum human malaria parasites, a field that should grow exponentially with the recent development of in vitro culture of P. knowlesi and P. cynomolgi (Kocken et al, 2002; Moon et al, 2013; Chua et al, 2019) combined with the use of genome editing techniques
The results demonstrated that P. knowlesi parasites recognize expression control sequences from evolutionary distant malaria species, such as the rodent malaria P. berghei and the laverania malaria P. falciparum
Summary
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. The lack of robust systems of long-term in vitro culture of P. vivax and the other human malaria parasites lagged the genetic manipulation of these species. We review the efforts to generate genetically modified non-falciparum human malaria parasites, in vivo and in vitro. The development of long-term in vitro culture of P. knowlesi in the 2000’s, using rhesus and human red blood cells, created a platform to genetically manipulate nonfalciparum malaria parasites. The use of CRISPR/Cas technology to genome edit P. knowlesi 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 P. falciparum
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