Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system

Ghorbal, Mehdi; Gorman, Molly; MacPherson, Cameron Ross; Martins, Rafael Miyazawa; Scherf, Artur; Lopez-Rubio, José-Juan

doi:10.1038/nbt.2925

Cited by 589 publications

(704 citation statements)

References 22 publications

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“…The inserted DNA encoded engineered antibodies that attack the malaria parasites. In the laboratory, this feature was extended to 99.5 percent of the offspring from matings between modified and unmodified mosquitoes [37][38][39].…”

Section: Crispr In the Treatment Of Hiv Infectionmentioning

confidence: 99%

CRISPR genome editing and its medical applications

Mahmoudian-Sani

Farnoosh

Mahdavinezhad

et al. 2017

Biotechnology & Biotechnological Equipment

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Genome editing has always been a challenging area as a means to provide more efficient ways to create a meaningful change in the genome. Today, the CRISPR (clustered regularly interspaced short palindromic repeat) restoration system is considered as one of the suitable and promising options for genome editing. This system has many advantages compared to the previous geneediting methods developed in this area. Compared to the previous systems, CRISPR can deactivate or eliminate a gene without interfering with intracellular mechanisms. The system can be used in the treatment of diseases and in related research with identifying the performance of defective genes in these diseases. CRISPR has more potentials and applications compared to previous systems. Among these applications, we can note the use of CRISPR in understanding genetic and epigenetic diseases such as cancer. Study of cancer by the CRISPR system is done by two approaches: turning off the oncogenes and turning on the tumour suppressor genes. According to the exact capability of CRISPR, this system can also be used to create exact mutations in different cell lines to model the cancers. This type of modeling can lead to a better understanding of cancer and the ability to develop effective drugs.

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Section: Crispr In the Treatment Of Hiv Infectionmentioning

confidence: 99%

CRISPR genome editing and its medical applications

Mahmoudian-Sani

Farnoosh

Mahdavinezhad

et al. 2017

Biotechnology & Biotechnological Equipment

View full text Add to dashboard Cite

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“…This technical advance could help to overcome certain regulatory hurdles associated with the use of transgenic crops. Finally, targeted nucleases have also been used to inactivate pathogenic genes to prevent viral (Lin et al 2014) or parasitic (Ghorbal et al 2014) infection, as well as to introduce knockin-specific factors capable of imparting pathogen resistance . Intriguingly, targeted nucleases could also serve as conduits for curbing mosquito-or insect-borne diseases through a technique known as gene drive (Burt 2003;Sinkins and Gould 2006), which harnesses genome editing to facilitate the introduction of a specific gene or mutation that can then confer a particular phenotype into a host and also be transmitted to its progeny (Windbichler et al 2011).…”

Section: Genome-editing Applications Engineering Cell Lines and Organmentioning

confidence: 99%

Genome-Editing Technologies: Principles and Applications

Gaj

Sirk

Shui

et al. 2016

Cold Spring Harb Perspect Biol

297

142

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Targeted nucleases have provided researchers with the ability to manipulate virtually any genomic sequence, enabling the facile creation of isogenic cell lines and animal models for the study of human disease, and promoting exciting new possibilities for human gene therapy. Here we review three foundational technologies-clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs). We discuss the engineering advances that facilitated their development and highlight several achievements in genome engineering that were made possible by these tools. We also consider artificial transcription factors, illustrating how this technology can complement targeted nucleases for synthetic biology and gene therapy.

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“…• groundbreaking genome-editing studies in vitro demonstrating that single-nucleotide changes in pfk13, mimicking GMS variants, alter P. falciparum DHA susceptibility in vitro [14,15]; • GWAS demonstrating the importance of genetic background, including novel alleles at several loci, in the K13-mediated phenotype [16].…”

Section: A New Artemisinin Susceptibility Phenotype Arises In Asiamentioning

confidence: 99%

Genetic markers of artemisinin resistance in Plasmodium spp. parasites

Sutherland

2017

Emerging Topics in Life Sciences

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The vast majority of malaria patients worldwide are currently treated with combination therapy comprising one of the artemisinin family of drugs, characterised by rapid action and short plasma half-life, co-formulated with a longer-lasting drug from the amino arylalcohol or quinoline families. There is now a widely perceived threat to treatment efficacy, as reduced susceptibility to rapid artemisinin clearance in vivo has become prevalent among populations of Plasmodium falciparum in the Greater Mekong subregion since 2008. In vitro and in vivo drug selection studies, heterologous cell expression experiments and genetic epidemiology have identified many candidate markers of reduced ring-stage susceptibility to artemisinin. Certain variants of the P. falciparum pfk13 gene, which encodes a kelch domain protein implicated in the unfolded protein response, are strongly associated with slow parasite clearance by artemisinin in the Mekong subregion. However, anomalies in the epidemiological association of pfk13 variants with true treatment failure in vivo and the curious cell-cycle stage specificity of this phenotype in vitro warrant exploration in some depth. Taken together, available data suggest that the emergence of P. falciparum expressing K13 variants has not yet precipitated a public health emergency. Alternative candidate markers of artemisinin susceptibility are also described, as K13-independent treatment failure has been observed in African P. falciparum and in the rodent malaria parasite Plasmodium chabaudi.

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Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system

Cited by 589 publications

References 22 publications

CRISPR genome editing and its medical applications

CRISPR genome editing and its medical applications

Genome-Editing Technologies: Principles and Applications

Genetic markers of artemisinin resistance in Plasmodium spp. parasites

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