Scientists have enhanced the efficiency of CRISPR/Cas9 gene editing by threefold using interstrand crosslinks, without resorting to viral material for delivery. This approach boosts the cell’s natural repair mechanisms, allowing for more accurate and efficient gene editing, potentially improving dis
Gene editing is a powerful method for both research and therapy. Since the advent of the Nobel Prize-winning CRISPR/Cas9 technology, a quick and accurate tool for genome editing discovered in 2012, scientists have been working to explore its capabilities and boost its performance.
In gene editing, this process uses the enzyme Cas9 as molecular “scissors” to snip sequences it recognizes, guided by the CRISPR system. This cut is also an opportunity to replace the severed genes with similar but improved ones, utilizing the cell’s natural repair mechanisms. If successful, the cell should have modified expressions and functions thereafter.
“Every workflow that we have put this approach into has worked better by roughly threefold,” Richardson said. Their discovery, like many breakthroughs in science, was actually something of a happy accident. While working to purify proteins to study DNA repair, graduate student researcher and lead author Hannah Ghasemi noted unanticipated changes to the outcomes of their experiments.
“What we think happens is that the cell detects and tries to repair the damaged DNA that we’ve added this crosslink to,” Richardson said. “And in doing so, it delays the cell past a checkpoint where it would normally stop this recombination process. And so by prolonging the amount of time that it takes the cell to do this recombination, it makes it more likely that the edits will go to completion.
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