CRISPR's New Partner
Scientists have found a new and smaller CRISPR gene editor called CasX
Dmitry Mazalevsky, Naked Science
For seven years, Cas9 has established itself as the chief gene editor used in experiments with plants, animals and bacteria for fast and accurate work with DNA, transformation and discovery of new ways to treat diseases. However, the CasX editor can seriously compete with it.
The protein, discovered two years ago by scientists from the University of California, Berkeley, Gill Banfield and Jennifer Dudna in some of the smallest bacteria, was similar to Cas9, but it was even smaller, which can be a great advantage when delivering it to the right cell.
According to a study published in the journal Nature (Liu et al., CasX enzymes compose a distinct family of RNA-guided genome editors), CasX really is a powerful and effective gene editor in both bacteria and human cells. Its structure is similar to Cas9 and its well–studied "cousin" – Cas12, and its differences seem to be due to evolution in bacteria, independently of other Cas proteins. Like Cas9, it can cut double-stranded DNA, bind to DNA to regulate genes, and target specific sequences.
In addition, since the editor was found in bacteria that humans do not have (Banfield extracted them from a database of microbes found in groundwater and sediments), the human immune system should accept it more easily than Cas9 accepts. However, some doctors fear that Cas9 may trigger an immune response in patients using CRISPR therapy.
"Immunogenicity, delivery capabilities and the specificity of the genome editing tool are all vital, and CasX demonstrates excellent performance in all these areas. In addition, the small size of CasX helps to clearly demonstrate the existence of the main path that nature uses. Understanding this pathway will help us better develop and develop genome editing tools for our purposes," says study co–author Benjamin Oakes.
The scientists used a cryo-electron microscope to take pictures of the CasX protein. Based on the unique molecular structure and shape of the protein, the researchers concluded that CasX evolved independently of Cas9, meaning they do not have a common ancestor.
According to Dudna, professor of molecular and cellular biology at the University of California, Berkeley, the culmination of biochemical experiments, genome editing and structural experiments in this study can serve as a vivid example of the comprehensive efforts undertaken by scientists. According to her, experts are not just looking for the next pair of molecular scissors, but intend to create a "Swiss army knife". In 2016, a group of researchers with the participation of specialists from Kobe University developed a genome editing technology based on CRISPR/Cas9 technology, which does not involve DNA splitting.
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