UC San Diego Engineers CRISPR Gene Drive That Spreads Through Bacteria to Strip Away Antibiotic Resistance
Researchers at the University of California San Diego have developed pPro-MobV, a second-generation CRISPR-based gene drive that spreads through bacterial populations via conjugal transfer to disable antibiotic resistance genes, demonstrating effectiveness even within biofilms.
Overview
Researchers at the University of California San Diego have developed a CRISPR-based genetic tool that can spread through bacterial communities and disable the genes responsible for antibiotic resistance, according to findings published in npj Antimicrobials and Resistance in February 2026. The system, called pPro-MobV, represents a second-generation approach that adapts gene drive technology — previously used in insect populations — to bacteria for the first time, offering a potential new strategy to combat a crisis projected to cause more than 10 million deaths annually by 2050.
The work was led by professors Ethan Bier and Justin Meyer of UC San Diego’s School of Biological Sciences, with contributions from collaborators in Victor Nizet’s group at UC San Diego’s School of Medicine. The study’s authors include Saluja Kaduwal, Elizabeth C. Stuart, Ankush Auradkar, Seth Washabaugh, Meyer, and Bier.
How pPro-MobV Works
Conventional approaches to fighting antibiotic resistance typically rely on developing new drugs or using CRISPR to cut and destroy resistance genes in individual bacteria. The pPro-MobV system takes a fundamentally different approach: rather than targeting bacteria one cell at a time, it exploits conjugal transfer — a natural process akin to bacterial mating — to spread its CRISPR components from cell to cell across an entire population.
The system works by inserting a genetic cassette into antibiotic resistance genes carried on plasmids, the small circular DNA molecules that bacteria frequently exchange and that serve as common vehicles for resistance traits. Once the cassette disrupts a resistance gene in one bacterium, it can transfer to neighboring cells through natural mating tunnels, creating a cascading effect that progressively strips resistance from the population and restores sensitivity to antibiotics.
The researchers also demonstrated that pPro-MobV components can be carried and delivered by engineered bacteriophages — viruses that naturally infect bacteria — providing an additional delivery mechanism that could evade bacterial defenses.
Biofilm Effectiveness
One of the most significant findings is that pPro-MobV functions within biofilms, the dense microbial communities that cling to surfaces in hospitals, medical devices, and environmental settings. Biofilms are notoriously resistant to conventional antibiotic treatment because their protective matrix limits drug penetration, making them a major factor in chronic and hospital-acquired infections. The ability of the gene drive to operate within these structures addresses one of the most persistent challenges in combating resistant infections.
From Insects to Bacteria
The pPro-MobV system builds on the original Pro-Active Genetics (Pro-AG) platform that Bier’s lab and Nizet’s group first described in 2019. That earlier system demonstrated that a CRISPR-based genetic cassette could be inserted into bacterial resistance genes with roughly 100,000-fold greater efficiency than conventional cut-and-destroy methods. The new second-generation system advances the concept by enabling the CRISPR components to spread autonomously through bacterial populations via conjugal transfer, rather than requiring direct introduction into each target cell.
“With pPro-MobV we have brought gene-drive thinking from insects to bacteria as a population engineering tool,” said Bier. Meyer described the technology as “one of the few ways that can actively reverse the spread of antibiotic-resistant genes,” distinguishing it from strategies that merely slow the emergence of new resistance.
Safety and Reversibility
The system incorporates a homology-based deletion mechanism designed to allow removal of the genetic cassette if needed, providing a built-in safety feature. This reversibility addresses a key concern with gene drive technologies: the potential for unintended ecological consequences if a self-propagating genetic element spreads beyond its intended target population.
Potential Applications
The researchers envision applications extending well beyond clinical settings. Approximately 50 percent of antibiotic resistance originates from environmental sources, including sewage treatment facilities, aquaculture operations, and agricultural feedlots where antibiotics are used extensively. A gene drive capable of spreading through bacterial populations in these environments could help reduce the reservoir of resistance genes before they reach clinical settings.
In healthcare, potential applications include addressing chronic biofilm-associated infections and supporting treatment of conditions where resistant bacteria have rendered standard antibiotics ineffective.
The research was supported by the Tata Institutes for Genetics and Society at UC San Diego, the National Institutes of Health, and the Howard Hughes Medical Institute Emerging Pathogen Initiative. Bier has disclosed a competing interest as co-founder of Agragene, a company working in related genetic technologies.