Scientists modify CRISPR to epigenetically treat diabetes and kidney disease in mice

By ASN Staff

"Salk scientists have created a new version of the CRISPR/Cas9 genome editing technology that allows them to activate genes without creating breaks in the DNA, potentially circumventing a major hurdle to using gene editing technologies to treat human diseases.

Most CRISPR/Cas9 systems work by creating "double-strand breaks" (DSBs) in regions of the genome targeted for editing or for deletion, but many researchers are opposed to creating such breaks in the DNA of living humans. As a proof of concept, the Salk group used their new approach to treat several diseases, including diabetes, acute kidney disease, and muscular dystrophy, in mouse models.

'Although many studies have demonstrated that CRISPR/Cas9 can be applied as a powerful tool for gene therapy, there are growing concerns regarding unwanted mutations generated by the double-strand breaks through this technology,' says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory and senior author of the new paper, published in Cell on December 7, 2017. 'We were able to get around that concern.'

To test the method, the researchers used mouse models of acute kidney injury, type 1 diabetes and a form of muscular dystrophy. In each case, they engineered their CRISPR/Cas9 system to boost the expression of an endogenous gene that could potentially reverse disease symptoms. In the case of kidney disease, they activated two genes known to be involved in kidney function, and observed not only increased levels of the proteins associated with those genes, but improved kidney function following an acute injury. For type 1 diabetes, they aimed to boost the activity of genes that could generate insulin-producing cells. Once again, the treatment worked, lowering blood glucose levels in a mouse model of diabetes."

Please read the full article for more information.

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"Salk scientists have created a new version of the CRISPR/Cas9 genome editing technology that allows them to activate genes without creating breaks in the DNA, potentially circumventing a major hurdle to using gene editing technologies to treat human diseases.

Most CRISPR/Cas9 systems work by creating "double-strand breaks" (DSBs) in regions of the genome targeted for editing or for deletion, but many researchers are opposed to creating such breaks in the DNA of living humans. As a proof of concept, the Salk group used their new approach to treat several diseases, including diabetes, acute kidney disease, and muscular dystrophy, in mouse models.

'Although many studies have demonstrated that CRISPR/Cas9 can be applied as a powerful tool for gene therapy, there are growing concerns regarding unwanted mutations generated by the double-strand breaks through this technology,' says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory and senior author of the new paper, published in Cell on December 7, 2017. 'We were able to get around that concern.'

To test the method, the researchers used mouse models of acute kidney injury, type 1 diabetes and a form of muscular dystrophy. In each case, they engineered their CRISPR/Cas9 system to boost the expression of an endogenous gene that could potentially reverse disease symptoms. In the case of kidney disease, they activated two genes known to be involved in kidney function, and observed not only increased levels of the proteins associated with those genes, but improved kidney function following an acute injury. For type 1 diabetes, they aimed to boost the activity of genes that could generate insulin-producing cells. Once again, the treatment worked, lowering blood glucose levels in a mouse model of diabetes."

Please read the full article for more information.

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Monday, December 11, 2017