Genetic diversity of Plasmodium falciparum and Plasmodium malariae and its association with infectivity of Anopheles coluzzii in the Mfou Health District, Central Region of Cameroon
Background Malaria remains a major public health challenge in Cameroon, with sustained transmission particularly in forest-savannah transition zones. Although Plasmodium falciparum is the predominant malaria parasite, non-falciparum species such as P. malariae also contribute to the human infectious reservoir and to onward transmission. Parasite genetic diversity and multiplicity of infection…
In a significant advancement for malaria research, scientists have developed a precise RNA-depletion system targeting Plasmodium falciparum, the parasite responsible for the most lethal form of malaria. This innovative approach, utilizing a high-fidelity Cas13d (HF-RfxCas13d), addresses limitations encountered in functional genomics due to the parasite's evolutionary lack of an endogenous RNA interference pathway.
By strategically integrating the HF-RfxCas13d expression cassette at the dispensable pfs47 locus, researchers created a stable transgenic line with constitutive cytosolic expression of HF-RfxCas13d. This development allowed for gene silencing without compromising the parasite's ability to grow and reproduce within host erythrocytes.
The researchers employed CRISPR-SpyCas9 to introduce single or dual guide RNAs (gRNAs) targeting three endogenous loci—ap4, ap2-exp, and ap2-g. This approach led to substantial mRNA depletion (ranging from 41% to 76%) of the targeted genes, offering a powerful tool for functional genomics in P. falciparum.
The system's application to the master transcriptional regulator of gametocytogenesis (ap2-g) showcased its potential. Depletion of ap2-g functionally impaired sexual differentiation in committed parasites, resulting in a notable 70% reduction in Sexual Conversion Rate. This breakthrough could accelerate the identification of potential drug targets and streamline malaria research efforts, providing a scalable and non-locus-modifying addition to the genetic toolbox for studying P. falciparum.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
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