ArticleGenome biology2015
Zinc finger nuclease-based double-strand breaks attenuate malaria parasites and reveal rare microhomology-mediated end joining.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Plasmodium falciparum DNA repair dynamics reveal unique roles for TLS polymerases and PfRad51 in genome diversification.Nucleic acids research · 2025Article
- Clinical challenges and technological breakthroughs in helminthic therapy for diabetes.Frontiers in immunology · 2025Review
- CRISPR/Cas9 and genetic screens in malaria parasites: small genomes, big impact.Biochemical Society transactions · 2022Review
- CRISPR-Cas Technology: Emerging Applications in Clinical Microbiology and Infectious Diseases.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Deletion of Plasmodium falciparum ubc13 increases parasite sensitivity to the mutagen, methyl methanesulfonate and dihydroartemisinin.Scientific reports · 2021Article
- Limited Plasmodium sporozoite gliding motility in the absence of TRAP family adhesins.Malaria journal · 2021Article
- An SR protein is essential for activating DNA repair in malaria parasites.Journal of cell science · 2021Article
- The contribution of extrachromosomal DNA to genome plasticity in malaria parasites.Molecular microbiology · 2021Article
- Phosphorylation of the Canonical Histone H2A Marks Foci of Damaged DNA in Malaria Parasites.mSphere · 2021Article
- Antimalarial Drug Resistance and Implications for the WHO Global Technical Strategy.Current epidemiology reports · 2021Review
- Evolutionarily distant I domains can functionally replace the essential ligand-binding domain ofeLife · 2020Article
- Vive la Différence: Exploiting the Differences between Rodent and Human Malarias.Trends in parasitology · 2020Review
- Cutting back malaria: CRISPR/Cas9 genome editing of Plasmodium.Briefings in functional genomics · 2019Review
- Quantification of wild-type and radiation attenuated Plasmodium falciparum sporozoite motility in human skin.Scientific reports · 2019Article
- Generation and functional characterisation of Plasmodium yoelii csp deletion mutants using a microhomology-based CRISPR/Cas9 method.International journal for parasitology · 2019Article
- Microtubule number and length determine cellular shape and function in Plasmodium.The EMBO journal · 2019Article
- Ribozyme-mediated, multiplex CRISPR gene editing and CRISPR interference (CRISPRi) in rodent-infectiousThe Journal of biological chemistry · 2019Article
- AFrontiers in cellular and infection microbiology · 2019Article
- Guide RNA selection for CRISPR-Cas9 transfections in Plasmodium falciparum.International journal for parasitology · 2018Article
- New and emerging uses of CRISPR/Cas9 to genetically manipulate apicomplexan parasites.Parasitology · 2018Review
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7 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundGenome editing of malaria parasites is key to the generation of live attenuated parasites used in experimental vaccination approaches. DNA repair in Plasmodium generally occurs only through homologous recombination. This has been used to generate transgenic parasites that lack one to three genes, leading to developmental arrest in the liver and allowing the host to launch a protective immune response. While effective in principle, this approach is not safe for use in humans as single surviving parasites can still cause disease. Here we use zinc-finger nucleases to generate attenuated parasite lines lacking an entire chromosome arm, by a timed induction of a double-strand break. Rare surviving parasites also allow the investigation of unconventional DNA repair mechanisms in a rodent malaria parasite.
resultsA single, zinc-finger nuclease-induced DNA double-strand break results in the generation of attenuated parasite lines that show varying degrees of developmental arrest, protection efficacy in an immunisation regime and safety, depending on the timing of zinc-finger nuclease expression within the life cycle. We also identify DNA repair by microhomology-mediated end joining with as little as four base pairs, resulting in surviving parasites and thus breakthrough infections.
conclusionsMalaria parasites can repair DNA double-strand breaks with surprisingly small mini-homology domains located across the break point. Timely expression of zinc-finger nucleases could be used to generate a new generation of attenuated parasite lines lacking hundreds of genes.
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