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Updated: Sep 3, 2025
CRISPR/Cas9 Gene Editing to Make Conditional Mutants of Human Malaria Parasite P. falciparum
Published on: September 18, 2018
CRISPR-Cas9 Editing of the Plasmodium falciparum Genome: Special Applications
Xu Zhang1, Kirk William Deitsch1, Ron Dzikowski2
1Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.
Abstract:
The virulence of Plasmodium falciparum has been attributed in large part to the expression on the surface of infected red blood cells of the variant surface antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Different forms of this protein are encoded by individual members of the multicopy gene family called var. Two attributes of the var gene family are key to the pathogenesis of malaria caused by P. falciparum; the hyperrecombinogenic nature of the var gene family that continuously generates antigenic diversity within parasite populations, and the ability of parasites to express only a single var gene at a time and to switch which gene is expressed over the course of an infection. The unique attributes of CRISPR-Cas9 have been applied to help decipher the molecular mechanisms underlying these unusual properties of the var gene family, both as a source of the DNA double strand breaks that initiate var gene recombination and as a way to recruit molecular probes to specific regions of the genome. In this chapter, we describe these somewhat unusual applications of the CRISPR-Cas9 system.
Insights
The CRISPR-Cas9 system aids in understanding Plasmodium falciparum virulence by investigating the var gene family. This research deciphers how antigenic diversity is generated and switched during malaria infections.
Area of Science:
- Molecular Biology
- Genetics
- Parasitology
Background:
- Plasmodium falciparum virulence is linked to the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant surface antigen.
- The var gene family encodes diverse PfEMP1 forms, crucial for malaria pathogenesis.
- var genes exhibit hyperrecombination, generating antigenic diversity, and allow single-gene expression with switching.
Purpose of the Study:
- To explore the application of CRISPR-Cas9 technology in studying the var gene family.
- To elucidate the molecular mechanisms behind var gene recombination and expression switching.
Main Methods:
- Utilizing CRISPR-Cas9 to induce DNA double-strand breaks, initiating var gene recombination.
- Employing CRISPR-Cas9 to recruit molecular probes to specific genomic regions for analysis.
Main Results:
- CRISPR-Cas9 facilitates the study of var gene recombination processes.
- The system aids in understanding the regulation of var gene expression and switching.
Conclusions:
- CRISPR-Cas9 offers unique applications for dissecting the complex genetics of malaria parasites.
- This approach provides insights into the generation and control of antigenic variation in Plasmodium falciparum.
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