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Gene Therapy

Safer Gene Editing Without Cleaving DNA

Posted on 29 August 2016

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Researchers have created a new genome editing technique called Target-AID, which induces point mutations instead of cutting DNA

Gene editing technology has fantastic potential, but there are remaining issues and questions over safety and specificity. The major contender is currently CRISPR-Cas9, but this induces a double stranded break in DNA which is a slightly riskier approach – particularly if it cuts in other locations too that you don’t want it to. Research teams across the world are both optimising and customising the CRISPR system; creating more accurate versions or versions that regulate gene expression as opposed to editing it.  One such team has now built an add-on to CRISPR, Target-AID. 

Credit: Image courtesy of Kobe University

Credit: Image courtesy of Kobe University

How does it work?

CRISPR traditionally involves a guiding RNA sequence attached to a cutting enzyme called Cas9. A mixed research team from Japan created a alternative synthetic complex; removing the ‘cutting’ nuclease activity of Cas9 and replacing it with a deaminase enzyme. Deaminases modify bases within nucleoside segments in DNA. 

Target-Aid switches the bases within DNA strands which can be either Cytosine, Adenine, Guanine or Thymine

Target-Aid switches the bases within DNA strands which can be either Cytosine, Adenine, Guanine or Thymine

This deaminase was proved to cause less cytotoxicity in cell culture, and also offers an alternative method of editing; one which causes less cellular stress and effort to repair double stranded breaks. While it may not be suitable for every editing task (especially those in which a large sequence requires insertion), for smaller editing tasks it could be a significant improvement over previous CRISPR techniques. 

Read more at ScienceDaily


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