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CRISPR is so popular even viruses may use it | Science

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The famous gene-editing tool CRISPR began as a bacterial defense against invading viruses. However, it turns out that the intended target has stolen his CRISPR for their own weapon. A new study reveals that thousands of bacteria-attacking viruses known as bacteriophages, or phages for short, contain the genetic sequences for her CRISPR system, deploying them against rival phages. It has been suggested that it is possible. This discovery proves the power of molecular weapons and may further enhance the value of his CRISPR as a gene-editing tool in the laboratory.

The discovery “opens the door to potential new applications for the CRISPR system,” says Mazhar Adli, a genomicist at Northwestern University Feinberg School of Medicine.

Like other viruses, phages cannot replicate on their own. Instead, they hijack the bacterium’s molecular machinery, often killing the host in the process. The CRISPR system allows bacteria to fight back. It contains repetitive stretches of DNA that match sequences of previously encountered phages. When these same phages attack the bacterium again, they use this repetitive DNA to encode RNA strands that manipulate partner enzymes that act like genetic scissors to target the phage at specific locations. Cleave the genome. For the past decade or so, scientists have worked to turn this immune defense into a gene-editing technique for myriad applications, including improving crop defense, detecting pathogens, and fighting diseases such as cancer.

Distinctive DNAs encoding components of the CRISPR system were previously found in a small number of phages. But scientists viewed these discoveries as mere “curiosities,” and she won the 2020 Nobel Prize in Chemistry for showing how to tune her CRISPR system to target specific sequences. said Jennifer Doudna, an award-winning structural biologist at the University of California, Berkeley. “But they wondered if these systems were more common.”

To find out, UC Berkeley geomicrobiologist Gillian Banfield and colleagues went looking for additional examples of CRISPR in the phage world. They looked at DNA taken from different environments rich in the virus’ bacterial hosts, including soil and the human mouth. The troll discovered over 6000 phages, including CRISPR System DNAscientists report online today cellThey also examined phage genome sequences posted to online databases and found many more instances of viruses carrying CRISPR. Although he has less than 1% of phages with this sequence, the researchers “didn’t expect the antiphage system to be so widely distributed within the phages,” Doudna said. increase.

Why do phages acquire evolved systems to stop them? The most likely reason, according to Doudna, is to beat the competition. Multiple viruses can attack a bacterium at the same time, triggering a “phage war” within an infected cell, she says. vulnerable to By subverting these rivals with her CRISPR system, phages can “completely monopolize the replication machinery,” she says.

Phages probably stole these CRISPR system sequences from microbial victims, she says. For example, some phages seem to have lost the ability to produce specific molecules that can kill bacteria. Presumably to protect the host in order to produce more phage.

Phage gene-editing technology may inspire new biotechnology. For example, most CRISPR-based approaches currently rely on the DNA-cleaving enzyme Cas9. However, Cas9 is so large that it cannot fit in some viruses used to genetically modify cells. But many phages boast a streamlined version known as Cas-lambda that is about 50 percent smaller, Doudna and Banfield’s team found. and others say that new gene-editing applications of CRISPR may be possible, but researchers must overcome several biotechnological hurdles first.

UC San Francisco microbiologist Joseph Bondy-Denomy notes that Doudna and Banfield “[John] Lennon-[Paul] McCartney” notes a level of synergy in hunting down so many CRISPR-bearing phages that no other scientist has been able to find. I want to see evidence that it does. I’m waiting to be discovered using CRISPR. “The next step is more,” he says.

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