Watch Out CRISPR-Cas9! There's a New and Smaller Gene Editor

Researchers believe the new protein called CasX could be better accepted by the human immune system.
Loukia Papadopoulos

Just last week, the scientific community saw the world's first CRISPR/Cas9-based approach to control genetic inheritance in a mammal. It was a big milestone indeed.

A better counterpart?

But now it seems Cas9 may have a rival and researchers are saying it is a smaller one. They are calling this new gene editor CasX.


It is not exactly entirely new. It was discovered two years ago by UC Berkeley scientists in the world’s smallest bacteria, but researchers were unsure if it would work outside its native environment.

However, new research is now revealing CasX is a viable alternative to Cas9. The gene editor was sourced from a microbe database found in groundwater and sediment, and it works in both bacteria and human cells.  

Better yet, scientists are arguing it may be more efficient than all its counterparts. 

“The immunogenicity, delivery, and specificity of a genome-editing tool are all vitally important,” said co-lead author Benjamin Oakes, a former UC Berkeley graduate student and current Entrepreneurial Fellow in the Innovative Genomics Institute.

“We’re excited about CasX on all of these fronts.”

CasX has all the capabilities of its cousin Cas proteins and then some. The researchers argue that because it comes from bacteria that are not found in humans, CasX should be better accepted by the human immune system, eliminating the fears that some doctors had regarding Cas9 triggering an immune reaction.

No common ancestors

In addition, according to an analysis made with a cryo-electron microscope, the researchers deduced that CasX evolved independently of Cas9.

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This means that the protein is truly unique sharing no common ancestor with its counterparts. As such, it could be used for applications completely different than those found in nature.

“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,” Oakes said.

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

Now, the scientists are busy exploring the many doors that were opened through this key discovery.

“We aren’t just looking to uncover the next pair of molecular scissors. We want to build the next Swiss Army knife," said Jennifer Doudna, IGI’s executive director, a UC Berkeley professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute Investigator. 

The study was published in the journal Nature.

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