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MIT and Broad scientists have overcome a key CRISPR-Cas9 genome editing hurdle: off-target editing errors.

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This is a significant improvement:

Researchers at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT have engineered changes to the revolutionary CRISPR-Cas9 genome editing system that significantly cut down on “off-target” editing errors. The refined technique addresses one of the major technical issues in the use of genome editing.

The CRISPR-Cas9 system works by making a precisely targeted modification in a cell's DNA. The protein Cas9 alters the DNA at a location that is specified by a short RNA whose sequence matches that of the target site. While Cas9 is known to be highly efficient at cutting its target site, a major drawback of the system has been that, once inside a cell, it can bind to and cut additional sites that are not targeted. This has the potential to produce undesired edits that can alter gene expression or knock a gene out entirely, which might lead to the development of cancer or other problems. 

In a paper published today in Science, Feng Zhang and his colleagues report that changing three of the approximately 1,400 amino acids that make up the Cas9 enzyme from S. pyogenes dramatically reduced “off-target editing” to undetectable levels in the specific cases examined. Zhang is the W.M. Keck Career Development Professor in Biomedical Engineering in MIT’s departments of Brain and Cognitive Sciences and Biological Engineering, and a member of both the Broad Institute and McGovern Institute.

Top Reddit comments:

This is really big news. Although the CRISPR technique was rather straightforward it was not very specific. Now with an engineered Cas9 the researchers have managed to drammaticaly improve its specificity. This has significant implications in using Cas9 for gene therapy etc. where specificity is very important!


I am beginning to think that we are getting close to a Cas9 system appropriate for human trials. At least for extracting human cells, modifying them, and then reintroducing them. Now when we get to the point of a safe vector that can introduce Cas9 directly into adult humans and modify a sufficient number of cells to cause desired changes, then we are really talking up a game changer.


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