Editing genes with a more precise alternative to CRISPR

CRISPR-Cas9 gene editing can cause unintended changes to the genome. A Yale team has developed an alternative that they believe will make gene editing more precise.

The gene editing technology with the most buzz these days is CRISPR-Cas9, which corrects genetic abnormalities by breaking two DNA strands and then inserting healthy genes or eliminating unhealthy ones. But this process can be dangerous: When the body mobilizes to repair those DNA breaks, errors can occur that create unwanted off-target effects.

A team of scientists at Yale has developed an alternative gene-editing technology that they say replaces CRISPR’s “hacksaw” effect with a more precise “scalpel.” They call it eukaryotic multiplex genome engineering (eMAGE), and it’s designed to to allow new genetic information to be inserted into DNA without requiring multiple double-strand breaks. They described the technology in the journal Cell.

Working in yeast, the Yale scientists engineered a DNA replication and repair method that allowed them to introduce limited genetic changes at multiple sites in the genome, according to a statement. They generated almost a million genetic variants, they said.

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“We can create lots of combinations of mutations, which gives us an unprecedented tool to identify driver mutations of disease and fundamentally reprogram cellular behavior," said senior author Farren Isaacs, associate professor of molecular, cellular and developmental biology at Yale in the statement.

RELATED: MIT scientists propose a safer way to edit genes with CRISPR

Gene editing continues to grab headlines around the world for its potential application to treating a range of genetic diseases. But its potential to permanently change the genome has raised fears about how unintended editing mistakes might harm patients.

Several CRISPR improvements have been proposed. Just last month, a team at the Broad Institute made headlines for developing a reversible gene editing system that’s based on targeting RNA. They tested their tool and found they could repair the mutations that cause Fanconi anemia and X-linked nephrogenic diabetes insipidus.

And just last week, MIT scientists showed they could eliminate the cholesterol-causing gene PCSK9 in mice by delivering CRISPR-Cas9 components into cells without the use of viral vehicles.

The Yale team intends to further develop their non-CRISPR system and prove out the concept in multicellular organisms.

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