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    Home > Biochemistry News > Biotechnology News > CRISPR+Covid=? Nature has discovered for the first time that the CRISPR protein can act as a multipurpose self-destruct system for bacteria

    CRISPR+Covid=? Nature has discovered for the first time that the CRISPR protein can act as a multipurpose self-destruct system for bacteria

    • Last Update: 2023-02-03
    • Source: Internet
    • Author: User
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    In this illustration based on cryo-electron microscopy images, the Cas12a2 protein unlocks the DNA double helix, allowing it to cut DNA single strands (blue and green).


    A protein recently discovered that can act as a multipurpose self-destruct system for bacteria, capable of degrading single-stranded RNA, single-stranded DNA, and double-stranded DNA, is the first self-destruct system
    in a genetic toolbox known as CRISPR.
    The study's authors said that because the discovery is able to target so many types of genetic material, it is possible to develop new cheap and highly sensitive at-home diagnostic tests
    for a variety of infectious diseases, including COVID-19, influenza, Ebola and Zika.

    The findings, published in the journal Nature, detail the new system
    in two papers.

    Using a high-resolution imaging technique called cryo-EM, the team found that when the protein, called Cas12a2, binds to a specific sequence of genetic material called target RNA, a potentially dangerous virus, one side of Cas12a2 swings out, showing an active site, similar to a switchblade
    .
    The active site then begins to indiscriminately cut any genetic material
    it comes into contact with.
    The researchers found that when a single mutation occurs in the Cas12a2 protein, the active site only degrades single-stranded DNA, a feature that is particularly useful
    when developing new diagnostics for various viruses.

    Tests based on this technology can theoretically combine the best features of PCR-based detection of viral genetic material (high sensitivity, high precision, and ability to detect active infections) with the best features of rapid home diagnostic tests (low production cost and no need for specialized laboratory equipment).

    It is also easily adaptable to any new RNA virus
    .

    David Taylor, associate professor of molecular biological sciences at the University of Texas at Austin and co-corresponding author of the new study, said: "If some new virus emerges tomorrow, all you have to do is figure out its genome, then change the guide RNA in the test, and then you can test it
    .
    "

    Such a diagnosis, which still requires separate work, could include collecting a patient's saliva or nasal sample and mixing it with the team's modified Cas12a2 protein, a piece of guide RNA that can identify specific viruses like a face photo, and a fluorescent probe that glows
    when its single-stranded DNA is cut.

    CRISPR is the name of a group of tools that occur naturally in bacteria and scientists have used it for gene editing
    .
    This is the first CRISPR protein
    to be found to degrade such a wide range of genetic material.

    "Cas12a2 basically grabs both ends of the DNA double helix structure and bends it tightly," says Jack Bravo, a postdoc at the University of Texas at Austin and co-first author of the paper, "so the middle helix suddenly opens and this active site can destroy the DNA fragments
    that become single-stranded.
    " This is where Cas12a2 differs from all other DNA-targeting systems
    .

    Co-corresponding authors of the paper are Ryan Jackson of Utah State University and co-first author Thomson Hallmark
    .
    Other co-authors are Bronson Naegle and Helmholtz Infection Research Center in Utah and Chase Beisel
    of the University of Würzburg, Germany.

    The structural data was collected using cryo-electron microscopy equipment at the Sauer Laboratory of Structural Biology at the University of Texas at Austin
    .

    The researchers filed a patent application for a modification of the Cas12a2 protein that enables it to cut only single-stranded DNA and use it for diagnosis
    .
    The Office of Technology Commercialization at the University of Texas at Austin is managing intellectual property and working to find industry partners
    who can help realize the technology's potential.

    Another paper in the same issue describes the biological functions of Cas12a2, and this article describes the mechanism
    by which this protein fulfills these functions.


    RNA targeting unleashes indiscriminate nuclease activity of CRISPR-Cas12a2


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