Global Technology - June 2018

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Using the gene-editing tool CRISPR to snip at DNA is akin to using scissors to edit a newspaper article. You can cut out words, but it’s difficult to remove individual letters or instantly know how the cuts affect the meaning of the text. In work that will help make the gene-editing process more precise, researchers at Stanford University, have developed a new kind of CRISPR platform called MAGESTIC barcodes. MAGESTIC stands for “Multiplexed Accurate Genome Editing with Short, Trackable, Integrated Cellular Barcodes.” This new platform makes CRISPR less like a blunt cutting tool and more like a word processor by enabling an efficient “search and replace” function for genetic material. Announced recently in a Nature Biotechnology paper, MAGESTIC also produced a seven-fold increase in cell survival during the editing process.

MAGESTIC is like the ‘find text” operation in a word-processing program; it also has a “replace-text” command allowing a desired change. This lets bioengineers really poke at the cell in a very precise way and see how the change affects cell function. Then, they can compare the actual effects of each variant with the computationally predicted effects, and ultimately improve models for predicting how genetic variants impact health and disease.

Being able to precisely edit genomes with CRISPR requires an extensive understanding of how cells will repair cuts at different sites across the genome so that you can control the process as needed. Currently, random mutations can occur at cut sites in the cell’s DNA, often because the DNA strands rejoin in unpredictable ways. What’s more, lots of cells don’t survive the editing process at all. Building accurate predictions for gene editing remains, therefore, extremely challenging.

What researchers want is a reliable way to program the CRISPR machinery to cut at desired locations throughout the genome, and then to direct the cells to introduce designed edits at the DNA cut sites. This can be done by providing the cell with a “donor” DNA that the cell’s DNA repair machinery can use as a template to replace the original sequence at the cut site. This is not unlike what editors often do to revise a text, first...

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