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Just How Safe Is Gene Editing? New Research Claims CRISPR Is More Accurate Than We Thought...


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Putting some fears to rest:

One of the biggest concerns about CRISPR was off-target binding, and whether this leads to any additional cuts to the sequence - which might lead to harmful mutation. It seemed likely CRISPR would form some interactions with other sites in the genome, but they didn't know if this was enough for the Cas9 enzyme to snip. The new research suggests it's not, and that while off-target binding does happen, it doesn't lead to a cut. 

"It's crazy that the Cas9 complex manages to scan the vast space of eukaryotic genomes. There is a lot of off-target binding by Cas9, but we found that these interactions are very brief—from milliseconds to seconds—before Cas9 moves on. If Cas9 bound for tens of seconds or minutes at each off-target site, it would never, ever be able to find a target and cut in a timely manner"

A triple check

The research showed that only when the correct sequence is found will the binding change the shape of Cas9 enough to allow it to edit a given sequence, like a proof-reading step. The Cas9 must recognise a PAM sequence (which occurs about 300 million times in the human genome), and the exact target sequence the RNA guide binds to, before it will clamp down and act. The team found that there's an added checkpoint too; the interaction must be long enough. If the sequence isn't a correct fit, it won't bind long enough to induce Cas9 activity. 

Looking ahead

This is positive news, and could herald more clinical trials involving CRISPR in the near future. There are also many other alternative enzymes to Cas9 in development or that already exist, which act in subtly different ways and may increase safety even further.  

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