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Cutting through resistance

How Locus Biosciences is using CRISPR-Cas3 to tackle antibiotic resistance

Most companies employing CRISPR-Cas9 for therapeutics are using it to edit human cells, but Locus Biosciences Inc. is betting the lesser-known CRISPR-Cas3 system will do a better job of treating bacterial infections and could be the long-sought solution to antibiotic resistance.

The company was launched two years ago to develop an antimicrobial platform that turns bacteria's natural CRISPR-Cas3 defense system against itself to eliminate specific pathogenic species while sparing human cells and the microbiome.

Locus has over $7 million in funding, which includes equity financing, a loan and a $5 million convertible note from the North Carolina Biotechnology Center and Chinese investor Tencent Holdings Ltd. The company hopes to close a series A round this fall -- at which point, the $5 million note would convert to equity --, giving it enough financing to bring it into the clinic.

The standard CRISPR approach uses the Cas9 endonuclease to make targeted double-stranded breaks in DNA and relies on the cell's natural, but imperfect, DNA repair mechanisms to disrupt individual genes by creating insertion-deletion mutations during the repair process. By contrast, the Cas3 exonuclease works by first nicking a target site, then chewing through the rest of the DNA, which destroys not only the DNA but the cells themselves.

For that reason, this system has been largely overlooked for human therapeutics, but it provides a unique advantage when targeting pathogens.

"Cas9 is the famous endonuclease because it has been good for making precise,

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