12:00 AM
 | 
Apr 24, 2014
 |  BC Innovations  |  Cover Story

CRISPR in the liver

Despite the fact that the therapeutic utility of CRISPR-based approaches has yet to be demonstrated, venture dollars keep flowing into new companies developing the platform. But proof of concept may come faster than expected as new findings show that a CRISPR-based compound can correct a mutation in adult mice with genetic liver disease.1

Last year, multiple independent teams adapted a newly identified bacterial defense system to create a platform for site-directed genome editing.2-7 The platform relies on a synthetic single guide RNA (sgRNA) to target the activity of the CRISPR (clustered, regularly interspaced short palindromic repeats)-associated bacterial endonuclease Cas9-the system is referred to in short as CRISPR-Cas9.

Cas9 introduces a double-strand break in genomic DNA in a location designated by complementary interactions between the sgRNA and the DNA target, which triggers DNA repair and genome editing.

Because editing specificity is driven by the sequence of the sgRNA, the CRISPR-Cas9 system is simpler and cheaper than other genome-editing tools, such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), which use engineered, DNA-binding proteins to site-specifically target DNA.

CRISPR-Cas9 has been applied in embryos to engineer mouse and nonhuman primate models of human disease.8,9 The platform also has been used to engineer complex mouse models by simultaneously introducing multiple gene mutations into embryonic stem cells.10,11

The first foray into therapeutic application occurred last year, when Editas Medicine was founded to use CRISPR-Cas9 to correct genomic defects in undisclosed diseases. Editas raised $43 million and brought together 5 scientific cofounders who spearheaded the conversion of the bacterial defense system to a programmable genome-editing tool.

Last week, the first CRISPR-Cas9 patent for genome-editing applications was assigned to the Broad Institute of MIT and Harvard and the Massachusetts Institute of Technology (MIT). The patent covers CRISPR-Cas9 systems engineered to work in eukaryotic cells, especially human cells, and methods of using these systems. For research use, the technology will be available to anyone on a nonexclusive basis. The Broad Institute did not disclose further licensing details.

Today, CRISPR Therapeutics, which aims to translate CRISPR-Cas9 into medicines with the potential to cure human genetic diseases, emerged from stealth mode. CRISPR Therapeutics was founded by Versant Ventures and raised $25 million.

Like Editas, CRISPR Therapeutics has not yet disclosed the specific targets or indications it will pursue.

CRISPR Therapeutics' scientific founders are Emmanuelle Charpentier, Daniel Anderson, Matthew Porteus, Chad Cowan and Craig Mello.

Charpentier is a professor at the Laboratory for Molecular Infection Medicine at Umeå University, the Helmholtz Centre for Infection Research...

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