Exciting new CRISPR-CasX variant could be ‘Swiss army knife’ for genetics

5 Feb 2019

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CRISPR-Cas9 has revolutionised gene editing, but a new variant of the technology may be far superior.

While discussions surrounding CRISPR-Cas9 of late have revolved largely around serious ethical questions, another topic of conversation on the technology is whether it can be improved.

Despite only being around for several years, CRISPR-Cas9 has shown itself to be a formidable gene editor in humans, plants, animals and bacteria, with the potential to open new avenues to treat disease. However, researchers at the University of California, Berkeley, have unveiled a new variant of the technology called CRISPR-CasX, which could be significantly more accurate and powerful than the original Cas9.

Discovered two years ago by one of its original inventors, Jennifer Doudna, and her colleague Jill Banfield, the CasX protein is similar to Cas9, but quite a bit smaller. This gives it a major advantage when you are trying to deliver a gene editor into a cell, but also outside its native bacteria.

Publishing its findings in Nature, the research team behind this discovery found that CasX is similar in design to Cas9 and its other well-studied cousin, Cas12, but is different enough to have evolved in bacteria independent of other Cas proteins. This means it can cut double-stranded DNA such as Cas9, bind to DNA to regulate genes and be targeted to specific DNA sequences like other Cas proteins.

Non-human in origin

Also, because it originates in non-human bacteria – dredged from a database of microbes found in groundwater and sediment – our immune systems should accept it easier than Cas9.

“The first thing that jumps out is how the highly unique domains accomplish similar roles to what we have seen with other RNA-guided, DNA-binding proteins. CasX’s minimal size, with no fat on the bone, helps to clearly demonstrate there is a basic recipe that nature uses,” said Benjamin Oakes, co-lead author of the study.

“Understanding this recipe will help us to better evolve and engineer genome-editing tools for our purposes rather than nature’s.”

Speaking of where CasX goes from here, Doudna said: “We aren’t just looking to uncover the next pair of molecular scissors. We want to build the next Swiss army knife.”

Colm Gorey was a senior journalist with Silicon Republic