Mon. Apr 22nd, 2019

They present a new CRISPR genetic editing tool

They present a new CRISPR genetic editing tool


The team of Jennifer Doudna, Professor of Chemistry and Molecular Biology at the University of California Berkeley, has presented this week in Nature a new gene editing tool lcalled CasX, who offers new features thanks to its smaller size than other enzymes such as Cas9.

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The announcement comes only a few weeks after Feng Zhang's rival group at the Broad Institute - with which Doudna maintains a legal battle over patents - announced a new CRISPR platform called Cas12b.

According to the UC Berkeley in a statement, in just seven years since its discovery by Doudna and his colleague Emmanuelle Charpentier, Cas9 "has proven to be a formidable editor of genes, used in humans, plants, animals and bacteria to cut and paste DNA quickly and accurately, transforming biology and opening new ways to treat diseases. "

Now CasX comes to join the CRISPR gene editing toolbox, which does not stop growing. The new enzyme was discovered two years ago by Doudna and Jill Banfield (also from UC Berkeley) in some of the smallest bacteria in the world, the protein was similar to Cas9, but with a smaller size. "A great advantage when it comes to introducing a gene editor in a cell," says Benjamin Oakes, one of the authors of the new study.

As detailed, "due to its small size, CasX is particularly suitable for therapeutic editing of the genome, since it can fit into the most commonly used delivery vehicle, the adeno-associated virus (AAV). This virus can introduce useful molecules into cells that harbor mutations that need repair, but it has a limited capacity. A smaller genome editing tool leaves room for other charges, such as the donor's DNA, "he argues.

Less immune reaction

In addition, because it comes from bacteria that are not found in humans - Banfield obtained it from a database of microbes found in groundwater and sediments - 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.

"The immunogenicity, delivery and specificity of a genome editing tool are of vital importance. We are excited about CasX on all these fronts, "says Oakes, who now works as an investor and entrepreneur at the Innovative Genomics Institute (IGI), created by Doudna.

The team used an electronic cryomicroscope to capture snapshots of the CasX protein through the editing movements of a gene. Based on the composition and unique molecular form of the protein, the researchers concluded that CasX evolved independently of Cas9, without sharing a common ancestor.

According to Jennifer Doudna, this new study is aa good example of the efforts your team is making in the field of genetic editing with CRISPR. "We're not just looking to discover new molecular scissors. We want to build the next CRISPR Swiss Army knife ».

The team of Spanish molecular biologist Guillermo Montoya is also working on this effort at the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen. His group successfully investigates the characteristics of different molecular scalpels to try to advance in the search for a multi-use CRISPR gene editing technology

For Benjamin Oakes, "the more tools there are, the more and the better the possibilities. We should not leave any stone unturned, since we are looking for the right tool for each job, "he concludes.

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