Modified CRISPR allows gene activation without editing DNA

Though the revolutionary gene editing tool CRISPR-Cas9 is best-known for helping scientists edit a strand of DNA more precisely and efficiently than ever before researchers have found another use for the CRISPR complex: changing what genes are expressed without altering the genome itself.

Researchers at the Salk Institute in San Diego have, for the first time been able to use CRISPR to activate beneficial genes in live mice suffering from muscular dystrophy, Type 1 diabetes and acute kidney injury.

In over 50 per cent of test cases, the health of the animals improved with the CRISPR intervention, according to a study published yesterday in the journal Cell.

According to scientists, earlier work had demonstrated that CRISPR could be used to alter gene expression in cells in a petri dish. The new study, however, represents the first time the technique has worked in a live animal, according to scientists.

''We moved this technique one big step toward human therapy,'' said Hsin-Kai Liao, a post-doctoral researcher at Salk and co-first author on the paper, reported.

Alexis Komor, a biochemist at UC San Diego who was not involved with the work said, ''This is a really thorough in vivo study that begins to bridge the gap between using CRISPR-based tools in cells in a dish and using them translationally.''

Meanwhile, the Salk Institute reported on its website, ''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.''