CRISPR/CAS9 genetic modification of plasmodium falciparum and transgenic parasites in malaria vaccine research

Marin Mogollon, C.Y.

For rodent malaria parasites the availability of a variety transgenic parasite lines expressing different reporter proteins under the control of stage-specific or constitutive promoters have been of great benefit to studies to reveal parasite gene function and to studies focussed on the evaluation of novel drugs and vaccines. The availability of similar transgenic P. falciparum reporter lines would also help to advance gene-function studies and studies aiming at development of new therapies for P. falciparum parasites. In this thesis, we describe a set of studies performed in P. falciparum to develop novel CRISPR/Cas9 methodologies to improve P. falciparum transgenesis and to create novel transgenic parasites that can be used to analyse host-pathogen interactions and for anti-malarial drug and vaccine research. We describe studies aiming at improving CRISPR/Cas9 genetic modification for introduction of transgenes into the genome of P. falciparum using a ‘neutral’ locus, a...Show moreFor rodent malaria parasites the availability of a variety transgenic parasite lines expressing different reporter proteins under the control of stage-specific or constitutive promoters have been of great benefit to studies to reveal parasite gene function and to studies focussed on the evaluation of novel drugs and vaccines. The availability of similar transgenic P. falciparum reporter lines would also help to advance gene-function studies and studies aiming at development of new therapies for P. falciparum parasites. In this thesis, we describe a set of studies performed in P. falciparum to develop novel CRISPR/Cas9 methodologies to improve P. falciparum transgenesis and to create novel transgenic parasites that can be used to analyse host-pathogen interactions and for anti-malarial drug and vaccine research. We describe studies aiming at improving CRISPR/Cas9 genetic modification for introduction of transgenes into the genome of P. falciparum using a ‘neutral’ locus, a disruption of the P230p gene using CRISPR/Cas9 showed that P230p like P230 and P48/45, has a vital role in P. falciparum male fertility and zygote formation and the creation of two chimeric P. falciparum parasites (Pf-PvCSP), where the gene encoding circumsporozoite protein (CSP), was replaced by two csp gene variants (VK210 and VK247) showing that species-specific features of CSP govern full sporozoite development.Show less

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CRISPR/CAS9 genetic modification of plasmodium falciparum and transgenic parasites in malaria vaccine research

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