CRISPR-Based Gene Drive Shows Promise in Combating Antibiotic Resistance
Antibiotic resistance (AR) is a rapidly escalating global health threat. As bacteria evolve to withstand treatments, “superbugs” are spreading, potentially leading to over 10 million deaths annually by 2050. Now, researchers are exploring advanced genetic technologies, including CRISPR gene editing and gene drive systems, to directly counter this resistance.
New CRISPR System Targets Resistance Genes
Researchers at the University of California San Diego have developed a new technology called pPro-MobV, building upon CRISPR gene editing and gene drive concepts. This system is designed to spread through bacterial communities and disable the genes responsible for antibiotic resistance. The team’s work, led by Professors Ethan Bier and Justin Meyer of the UC San Diego School of Biological Sciences, aims to neutralize AR in large populations by introducing a few modified cells.1
How pPro-MobV Works
The foundation of this technology began in 2019 with the development of the original Pro-AG system, which introduced a genetic cassette into bacteria to shut down antibiotic resistance genes.2 This cassette targets resistance genes carried on plasmids – modest circular DNA molecules within bacterial cells – disrupting their function and restoring antibiotic sensitivity.
The newer pPro-MobV system utilizes conjugal transfer, a process akin to bacterial mating, to move CRISPR components between cells. This allows the resistance-disabling elements to distribute across populations. Importantly, the system has been shown to function effectively within biofilms – dense microbial communities that are particularly resistant to conventional cleaning and antibiotic treatments.2
Expanding the Reach with Bacteriophages
Researchers have similarly found that elements of the pPro-MobV system can be transported by bacteriophages (phage), viruses that infect bacteria. Engineered phage are already being developed to combat antibiotic resistance by delivering disruptive genetic material into bacterial cells. Combining pPro-MobV with these engineered phage could amplify the impact.2
Safeguards and Reversibility
The platform includes a safeguard – homology-based deletion – allowing scientists to remove the inserted genetic cassette if necessary.2 This technology offers a unique approach to actively reversing the spread of antibiotic-resistant genes, rather than simply slowing it down.
The Growing Threat of Antimicrobial Resistance
A recent study published in The Lancet forecasts that more than one million people died from antimicrobial resistance globally each year between 1990 and 2021, and projects a 70% increase in deaths by 2050 compared to 2022.1 Another study estimates that antimicrobial resistance could be associated with a cumulative 169 million deaths from 2025 to 2050.2 The impact will vary by age and location, with South and Southeastern Asia and sub-Saharan Africa expected to experience a higher burden of AMR-related deaths.
Antimicrobial resistance is projected to be one of the biggest global health threats.4
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