Chinese scientists have developed new genetic manipulation tools for Plasmodium falciparum

Chinese scientists have developed new genetic manipulation tools for Plasmodium falciparum

January 07, 2019 Source: Ministry of Science and Technology

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Malaria is listed as the world's three major infectious diseases along with AIDS and tuberculosis. Plasmodium is the causative agent of malaria, of which Plasmodium falciparum has the highest mortality rate. Genetic manipulation at the molecular level is an important means to study the pathogenesis of the Plasmodium falciparum and the mechanism of drug resistance. However, gene editing by homologous recombination in Plasmodium falciparum is extremely inefficient, and Plasmodium falciparum lacks the key elements for gene editing using RNAi methods. Therefore, research on Plasmodium falciparum is urgently needed to be efficient and simple. Genetic manipulation tools.

Under the support of the national key research and development program “Protein machinery and life process regulation”, the research team of the Shanghai Pasteur Institute of the Chinese Academy of Sciences developed a new genetic manipulation tool for Plasmodium falciparum. The research team used the CRISPR/dCas9 system to fuse dCas9 with two epigenetic modification enzymes (acetyltransferase and deacetylase) of Plasmodium falciparum. Under the guidance of specific sgRNA, dCas9 recombinant protein was used in the target gene. A specific transcriptional initiation site (TSS) regulates the level of chromatin histone acetylation, thereby controlling the silencing or activation of this gene expression, and successfully constructing a novel genetic manipulation tool based on epigenetic modification in Plasmodium falciparum . Using this new genetic manipulation tool, the team successfully regulated the two key genes PfRh4 and PfEBA-175 of P. falciparum infection in human red blood cells and induced changes in the corresponding infection phenotype. This research provides a powerful and effective genetic manipulation tool for functional genomics research of Plasmodium falciparum. Related research results were recently published in the PNAS journal.

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