Move over, CRISPR/Cas9! I’ve been enthusing about CRISPR for a while now, with the caveat that Cas9 is not accurate enough for editing in humans, with far too high a likelihood of cutting the wrong sections of DNA, leading to damaging breakages. People using CRISPR/Cas9 to edit human DNA should think twice right now. However, there’s a potential new Cas protein on the block: Cas3. Instead of cutting the DNA, Cas3 goes ahead and deletes large stretches of DNA — up to 100 kilobases of it.
I haven’t got access to the full paper right now, but the ScienceDaily post suggests that the major therapeutic value is that this can be used to remove viral DNA insertions, such as that of the herpes simplex virus. Despite other things around the internet claiming Cas3 is more accurate, I haven’t so far seen any evidence to suggest that’s the case. It has the same limitations as Cas9 in that the recognition of the target DNA needs to be absolutely precise. If the binding isn’t correct, large stretches of necessary DNA could be erased. One of the paper’s authors admits as much in the ScienceDaily article: this is still a limit on therapeutic uses for CRISPR. It’s more than the “shortcoming” Ke calls it: it’s an absolute dealbreaker.
It’s also worth remembering that we currently have no way to ensure CRISPR edits DNA in the correct cells, and in all the required cells, in a human body. At the moment, gene editing will be solely on the germline, before there are trillions of cells in need of edits.
Still, Cas3 will most likely be a valuable tool in the arsenal, alongside Cas9, for precision gene editing. We just need to solve the issues of targeting and specificity first. If nothing else, it’s solid proof that there’s more than one Cas protein available to do the job!