Researchers at the University of California San Diego report they have developed a second-generation CRISPR-based “Pro-Active Genetics” system, called pPro-MobV, that is designed to spread between bacteria and disable antibiotic-resistance genes, including inside hard-to-treat biofilms.
Antibiotic resistance has been described by UC San Diego as an accelerating global health crisis, with projections that drug-resistant “superbugs” could be responsible for more than 10 million deaths worldwide each year by 2050.
UC San Diego said the new work comes from the laboratories of School of Biological Sciences professors Ethan Bier and Justin Meyer, who developed a gene-drive-like approach for bacteria. The system—described as a second-generation Pro-Active Genetics (Pro-AG) platform and named pPro-MobV—is intended to spread through bacterial communities and disable genes that confer antibiotic resistance.
“With pPro-MobV we have brought gene-drive thinking from insects to bacteria as a population engineering tool,” Bier said in the university’s account. “With this new CRISPR-based technology we can take a few cells and let them go to neutralize AR in a large target population.”
According to the university, the idea builds on an earlier Pro-AG concept developed in 2019 in collaboration with UC San Diego School of Medicine professor Victor Nizet’s group. In that earlier work, a genetic cassette was introduced into bacteria and designed to copy itself to inactivate antibiotic-resistance genes. The cassette targets resistance genes carried on plasmids—small circular DNA molecules inside bacteria—so that disrupting those genes can restore sensitivity to antibiotics.
In the new version, UC San Diego said pPro-MobV spreads key CRISPR components via conjugal transfer, a process it likened to bacterial mating. The researchers reported that the system can move through bacterial biofilms—dense communities of microbes that can be difficult to remove—and that this biofilm setting is important because it can make bacterial growth harder to overcome in clinical and enclosed environments.
“The biofilm context for combating antibiotic resistance is particularly important since this is one of the most challenging forms of bacterial growth to overcome in the clinic or in enclosed environments such as aquafarm ponds and sewage treatment plants,” Bier said. “If you could reduce the spread from animals to humans you could have a significant impact on the antibiotic resistance problem since roughly half of it is estimated to come from the environment.”
UC San Diego also said elements of the system can be carried by bacteriophages—viruses that infect bacteria—and that the team envisions pPro-MobV working alongside phages being engineered to combat antibiotic resistance. As an additional safeguard, the platform can incorporate a “homology-based deletion” process intended to allow removal of the inserted gene cassette if needed.
“This technology is one of the few ways that I’m aware of that can actively reverse the spread of antibiotic-resistant genes, rather than just slowing or coping with their spread,” Meyer said.
The work was published in npj Antimicrobials and Resistance in 2026 in a paper titled “A conjugal gene drive-like system efficiently suppresses antibiotic resistance in a bacterial population.”
