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CRISPR is used to modify viruses and create new weapons against superbugs: shots



About two years ago, Alphonso Evans went to hospital for another bladder infection and ended up in intensive care. To fight antibiotic-resistant superbugs, scientists have developed "living antibiotics" that consist of genetically engineered viruses and use the CRISPR gene editing tool.

Rob Stein / NPR


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Alphonso Evans rolls his wheelchair into a strength machine at the Charlie Norwood VA Medical Center's gym in Augusta, Georgia.

"I'm not so worried about dying from a heart attack or diabetes because I'm active, I know what I have to do to tackle it: watch out for what I eat," says Evans , "But what do I do with an infection or fight off a bacterium ̵

1; something in me that I only see when it's too late?" from his hands. And like many patients with spinal cord injuries, it is prone to infections, especially bladder infections.

About two years ago he came to the VA Medical Center because of what he thought was further cystitis. It turned out that he also had a bone infection and got pneumonia. He ended up in intensive care. "It scared me," says Evans, who lives near Hephzibah, Ga. "And I'm not afraid of that."

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

I come to the point where there are organisms that are resistant to any known antibiotic, "says Michael Priebe, a physician who leads the spinal cord injury service at the VA Medical Center.

" I am afraid that When we are in the race, we can no longer keep up with the enemy – the resistant bacteria. The Superbugs take control, and we have nothing left to defend against, "says Priebe.

So Priebe has recruited Evans to help Develop another way to fight Superbugs, it's a novel living antibiotic Viruses that were genetically engineered with the gene editing tool CRISPR.

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

Dr Michael Priebe and his colleagues plan to produce cocktails over the year with billions of bacteriophages genetically engineered with CRISPR to infuse into six centers The United States.

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Later this year, Drs. Michael Priebe and his colleagues infuse cocktails containing billions of CRISPR genetically engineered bacteriophages into six US centers.

Rob Stein / NPR

"If we succeed, it will revolutionize the treatment of infections," he adds. "This can be the trailblazer that gets us out of this arms race with the resistant bacteria and allows us to use a completely different mechanism to fight the pathogenic bacteria that infect us."

Locus Biosciences of Morrisville, NC, is concerned with viruses known as bacteriophages (called phages for short). Phages are the natural enemies of bacteria. They can infect and destroy bacteria by proliferating in large numbers until the microbes literally explode.

Locus scientists have created a cocktail of three phages modified with CRISPR discovered by studying the immune system of bacteria.

"We've learned to reprogram this immune system to attack itself," says Paul Garofolo, CEO of the company. "We charge the viruses with CRISPR constructs that essentially work like small pac-men, get into a target bacterial cell and chew the DNA of that target, making them much more effective killers."

Locus is one of several companies trying to combat health problems with CRISPR by fighting only bad bacteria in the body and leaving the good guys alone.

"I think it's really exciting," says Steffanie Strathdee, the phage at the University of California San Diego. "We've used antibiotics that really take a scorched-earth approach to treating infections, not only killing the bacteria we want to kill, they also kill friendly bacteria in our microbiome."

The microbiome contains the trillions of friendly microbes that live in the human body.

"The potential lies in caring for the microbiome – weeding out unhealthy bacteria and promoting the growth of healthy bacteria in our microbiome," wrote Strathdee's book The Perfect Predator, about a final bacteriophage treatment to save her husband.

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

"I think it's a fascinating approach, it's a kind of really smart approach," says Graham Hatfull, a professor of life sciences at the University of California, University of Pittsburgh, specializing in phage research. He was part of a team that recently used genetically engineered phages to treat Superbug infection for the first time.

Hatfull fears, however, that there is not enough research to date to really understand bacteriophages.

"In a sense, the use of artificial phages is a bit like running before you can walk in. It's difficult to improve something without knowing how to try to improve work," says Hatfull.

And there is always the possibility that it backfires.

"The worry is that you could basically turn harmless bacteria into potentially dangerous ones," says Hatfull.

Priebe admits there could be dangers and say that's why the initial tests are primarily aimed at ensuring the safety of CRISPR-modified phages.

"We have to take things slowly," says Priebe. "We do not know how things will turn out."

Later that year, he and his colleagues plan to infuse patients like Evans twice a day for seven days to infuse six cocktails with billions of CRISPR-engineered phages in the United States.

The study will involve 30 patients. Twenty of them receive the engineered phage cocktail and ten a placebo. The researchers will then follow the volunteers and perform extensive tests of their blood and urine to determine if the approach is safe and affects the levels of E. coli bacteria in their urinary tract. In this case, the company is planning further research to find out how well the approach could fight infection.

In preparation for the study, Priebe plans to examine about 200 paralyzed patients, including Evans, to gain better insight into the natural course of E. coli colonization of the urinary tract in paralyzed patients.

Evans says he is also willing to volunteer for the treatment phase of Priebes research.

"I think that's a great idea," he says.

Evans 25 years military service, including a tour to Vietnam and stations in South Korea and Germany. But he was not paralyzed when he was fighting abroad.

"That's ironic," says Evans. "Twenty-five years in the army and never hurt." Nothing. "Two days before I retired, I drove down the street, this kid shot at cars and he shot me in the back."

Since then he has been struggling with medical issues, including repeated urinary tract infections.

"The very fact that research is in progress gives us hope," says Evans.


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