A patient who was on the brink of death after being infected with E. coli survived thanks to a virus. The E. coli was a superbug resistant to existing antibiotics, but it could not withstand a bacteriophage virus that infects bacteria and was armed with CRISPR-Cas9.
Saima Aslam, a professor at the University of California, San Diego (UCSD) School of Medicine, and her team said on the 11th in the international journal Clinical Infectious Diseases that "a 65-year-old male patient who had received a kidney transplant deteriorated after being infected with antibiotic-resistant E. coli, then recovered after receiving a bacteriophage virus equipped with CRISPR-Cas9."
◇ Treating a patient infected with resistant bacteria after a kidney transplant
Bacteriophages, viruses that use bacteria as hosts, were first discovered in India in 1896 by British bacteriologist Ernest Hankin. In 1917, French microbiologist Félix d'Hérelle gave them their current name from Greek, meaning "eats bacteria." They are commonly called phages. Recently, artificial intelligence (AI) created new bacteriophage viruses in the same way as ChatGPT, drawing global attention.
The patient who received the phage procedure this time was infected with the superbug E. coli a few months after a kidney transplant. No antibiotic worked, a large mass grew in the patient's bladder, and an open wound formed on the abdomen. Aslam's team, unable to clear the infection with standard treatments, tried a phage therapy developed by SNIPR Biome, a Danish biotech corporations.
A bacteriophage virus attaches to a bacterium, punches a hole in its surface, and injects its own genetic DNA inside. Using the bacterium's replication enzymes, the DNA replicates its genes and capsid proteins. The numerous progeny bacteriophages then lyse the bacterium and emerge.
The bacteriophage virus used this time was equipped with CRISPR-Cas9 to selectively kill only E. coli. The team said that one week after starting bacteriophage therapy for the E. coli infection, the open wound began to heal. The bladder mass volume shrank by half, from 0.74 L (liter) to 0.37 L.
This is the first time a bacteriophage procedure equipped with CRISPR-Cas9 has succeeded. Eric van der Helm of SNIPR, a co-author of the paper, said, "It is too early to conclude from a single case that a CRISPR-Cas9-equipped bacteriophage eliminated antibiotic-resistant bacteria," adding, "It is possible that a synergy came from the combination of the bacteriophage and a new antibiotic used beforehand."
◇ Gene scissors that selectively destroy only E. coli
Thanks to their ability to kill bacteria, bacteriophages were used in the 1920s and 1930s to treat various bacterial diseases such as dysentery and sepsis. As penicillin antibiotics became widely used in the 1940s, they were forgotten, but as antibiotic-resistant bacteria have surged like now, they are again drawing attention as therapeutics.
SNIPR Biome developed SNIPR001, a therapy that adds CRISPR-Cas9 to bacteriophages. CRISPR-Cas9 is an enzyme complex that freely cuts DNA. It typically consists of a guide RNA that finds and zips onto the target DNA to be cut, and Cas9, an enzyme protein that cuts at the bound site.
SNIPR loaded a CRISPR-Cas9 that seeks only E. coli DNA into the bacteriophage. Also, whereas conventional CRISPR-Cas9 contains the Cas9 enzyme that cuts DNA, the gene scissors inserted into the virus are equipped with the Cas3 enzyme that outright degrades E. coli DNA. It is like creating a powerful guided missile that finds only E. coli and completely destroys it.
Ironically, CRISPR-Cas9 originally came from an immune system in which bacteria remember the genes of attacking viruses and cut them immediately upon re-encounter. Scientists effectively repurposed the bacteria's defensive weapon to hunt bacteria.
The company plans to definitively demonstrate the efficacy of the phage virus equipped with CRISPR-Cas9 through additional clinical trials. It said it has already received 12 requests for patient-funded clinical trials like this one. In the United States, it is conducting a phase 2 clinical trial with the same phage virus in patients receiving cancer treatment. Some cancer therapies increase the risk of E. coli infection.
References
Clinical Infectious Diseases (2026), DOI: https://doi.org/10.1093/cid/ciag446