From bench to biome: CRISPR phages could precision edit the microbiome
CRISPR-engineered bacteriophages may offer a way to edit the microbiome in situ by delivering a targeted payload directly to select microbes in the gut.
During a presentation at Probiota Americas 2026 in Vancouver, John Beckley, a PhD Candidate in the group of renowned CRISPR scientist Dr. Rodolphe Barrangou at North Carolina State University, explained that application of this technology for therapeutic purposes is close, but any potential use in dietary supplements is a long way away.
CRISPR, which is short for “clustered regularly interspaced short palindromic repeats”, is a method for genome editing. It hit the headlines a couple of years ago when Emmanuelle Charpentier and Jennifer Doudna were awarded the 2020 Nobel Prize in Chemistry for their discovery of the CRISPR/Cas9 genetic scissors.
CRISPR-Cas systems occur naturally in about half of the bacteria that exist in the world and have been used in the dairy industry for years to enhance phage resistance in cheese and yogurt cultures, for example.
Dr. Barrangou’s group has made significant advances over the years to CRISPR engineer probiotics, including Bifidobacteria.
“A lot of the CRISPR engineering we do, especially in probiotics, we’re doing on the bench, so we have a lot of DNA that we’re putting into the bacteria,” said Beckley. “We have these sophisticated equipment that we use to get the DNA inside, but that doesn’t really apply when we’re trying to edit or engineer microbes that are in their native context, so in situ, and so we want to be able to develop methods for delivery that are biological.
“Phages are a good way to do that.”
Phages can then deliver an engineered DNA payload directly to bacteria in the gut that includes the CRISPR machinery. Inside bacteria, this CRISPR payload can then edit the genome to modify or remove specific genes in situ.
Safety
While this may sound scary to some people, Beckley noted that CRISPR is FDA-approved for treating human cells, and there are lots of trials in place for treating bacteria, including using CRISPR-engineered phages.
The phages can also be manipulated to prevent their spread beyond the specific target bacteria.
Despite the huge promise, CRISPR-engineered phages in dietary supplements are not going to be appearing on store shelves any time soon, he said.
“Phages that have CRISPR put in them are currently in clinical trials to treat bacterial infections, UTIs, things like this, so it’s really close. So, I think there’s opportunity to use these from a therapeutic standpoint,” he said. “I think it takes a little bit longer to get to the point where we’re using them more as like something that’s not treating a disease, so something that could potentially modulate short chain fatty acids or secondary bile acids in the gut. I think that takes a little bit longer for us to understand the complex dynamics that are happening within the microbiome.”
Watch the video for the full interview.
