A new gene-editing protein, CasX, may give CRISPR-Cas9 a run for its money. Berkeley scientists have determined the unique structure of CasX (grey), revealing that this pint-sized Cas enzyme is dominated by RNA (red) that directs it to specific sequences of DNA (blue), where it binds and cuts the DNA.
CasX is, in fact, a potent and efficient gene editor in both bacteria and human cells. Its design is similar to Cas9 and its well-studied cousin, Cas12, but it is different enough that it appears to have evolved in bacteria independently of the other Cas proteins.
It can cut double-stranded DNA like Cas9, can bind to DNA to regulate genes, and it can be targeted to specific DNA sequences like other Cas proteins.
Plus, because it comes from bacteria that are not found in humans Banfield dredged them from a database of microbes found in groundwater and sediment, the human immune system should accept it more easily than Cas9.
Some doctors fear that Cas9 may create an immune reaction in patients treated with CRISPR therapies.
Co-lead authors Jun-Jie Liu and Natalia Orlova used a cryo-electron microscope to capture snapshots of the CasX protein going through the motions of editing a gene.
Based on the protein’s unique molecular makeup and shape, the researchers concluded that CasX evolved independently of Cas9, sharing no common ancestor.
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.”