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CRISPR system opens window to C. albicans pathology
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Massachusetts researchers have developed a CRISPR-Cas system that allows them to systematically edit the Candida albicans genome, which could lead to new antifungal targets, according to study data.
Because it is diploid, has no plasmid system or meiotic phase, C. albicans has been a difficult pathogen to study, Valmik K. Vyas, PhD, and colleagues at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, said.
“We have developed a [clustered regularly interspaced short palindromic repeats (CRISPR)] system in C. albicans that overcomes many of these roadblocks by permitting efficient genome editing,” the researchers wrote in Science Advances.
The system, which consists of a Candida-compatible Cas9 nuclease and a synthetic guide RNA (sgRNA), generates homozygous mutations of a target gene in a single transformation.
“The ability to analyze essential genes provides an opportunity to explore potential antifungal targets,” the authors wrote.
The researchers created two systems: a “Duet system,” in which two plasmids are integrated and a “Solo system,” which combines the CRISPR system and the sgRNA system in a single plasmid structure.
Vyas and colleagues used the CRISPR system in laboratory and clinical strains of C. albicans. They mutated both copies of several genes, most notably members of a gene family critical to antibiotic resistance as well as an essential gene, according to a Whitehead Institute press release. The researchers estimated that the modified CRISPR system will be capable of targeting more than 98% of the C. albicans’ genome.
Gerald R. Fink
“The ability to engineer Candida albicans with CRISPR technology has changed the playing field,” Gerald R. Fink, PhD, professor of biology at Massachusetts Institute of Technology and a founding member of the Whitehead Institute, said in the release. “We used to attack this human pathogen with our hands tied behind our back. Our findings cut these bonds, freeing us to forge ahead on problems in basic research and human health.” – by Colleen Owens
Disclosure: The researchers report no relevant financial disclosures.
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