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November 15, 2023
May 23, 2019
November 15, 2023
May 23, 2019

Scientists Modify Viruses With CRISPR To Create New Weapon Against Superbugs

About two years ago, Alphonso Evans went to the hospital for what he thought was just another bladder infection and ended up in intensive care. In an effort to combat antibiotic-resistant superbugs, scientists have created "living antibiotics" made of viruses that have been genetically modified using the gene-editing tool CRISPR. Rob Stein/NPR

Alphonso Evans rolls his wheelchair into a weight machine in the gym at the Charlie Norwood VA Medical Center in Augusta, Ga.

"I'm not so much worried about dying from a heart attack or diabetes, because I'm active. I know what to do to work against it: watch what I eat, exercise," Evans says. "But what do I do about an infection? Or fighting off a bacteria — something inside me that I don't see until it's too late?"

Evans, 67, is fully paralyzed from the chest down and has only partial use of his hands. And like a lot of spinal cord injury patients, he's prone to infections, especially bladder infections.

About two years ago, he came to the VA medical center for what he thought was just another bladder infection. Turns out, he also had a bone infection and developed pneumonia. He ended up in intensive care. "It scared me," says Evans, who lives nearby in Hephzibah, Ga. "And I don't scare easy."

Bladder infections, like many others, are increasingly becoming resistant to antibiotics.

"We are getting to the point where there are organisms that are resistant to every known antibiotic," says Michael Priebe, a doctor who heads the spinal cord injury service at the VA medical center.

"My fear is that as we are in this arms race, there gets to the point where we are not able to keep up with the enemy — the resistant bacteria. The superbugs take over, and we have nothing to defend against it," Priebe says.

So Priebe enlisted Evans to help develop a different way to fight superbugs. It's a new kind of living antibiotic made out of viruses that have been genetically modified using the gene-editing tool CRISPR.

"What CRISPR is able to do is something that we've not been able to do before. And that is, very selectively modify genes in the viruses to target the bacteria," Priebe says.

"If we're successful, this revolutionizes the treatment of infections," he adds. "This can be the game changer that takes us out of this arms race with the resistant bacteria and allows us to use a totally different mechanism to fight the pathogenic bacteria that are infecting us."

The approach, developed by Locus Biosciences of Morrisville, N.C., involves viruses known as bacteriophages (called phages for short). Phages are the natural enemies of bacteria. They can infect and destroy bacteria by reproducing in large numbers inside them until the microbes literally explode.

Locus scientists have created a cocktail of three phages that have been modified using CRISPR, which was discovered by studying the immune systems of bacteria.

"What we've learned how to do is reprogram that immune system to attack itself," says Paul Garofolo, the company's CEO. "We load the viruses up with CRISPR constructs, which essentially work like little Pac-Men. They go into a target bacteria cell, and they chew up the DNA of that target. It makes them much more potent killers."

Locus is one of several companies that are trying to use CRISPR to fight health problems by targeting only bad bacteria in the body and leaving the good ones alone.

"I think it's really exciting," says Steffanie Strathdee, who studies phages at the University of California San Diego. "We've been using antibiotics, which really have a scorched-earth approach to the treatment of infections. They don't just kill the bacteria that we want to kill. They kill friendly bacteria in our microbiome as well."

The microbiome comprises the trillions of friendly microbes that inhabit the human body.

"The potential is to groom the microbiome — to weed out unhealthy bacteria and to promote the growth of healthy bacteria in our microbiome," says Strathdee, who wrote the book The Perfect Predator, about a last-ditch bacteriophage treatment to save her husband.

Other scientists agree that the strategy is promising, especially given the threat posed by superbugs.

This article was originally published in NPR. Continue reading the full story here: