CRISPR/Cas9 technology in Galleria mellonella (greater wax moth) enables precise gene editing and the generation of transgenic lines, enhancing its use as an ethical, low-cost in vivo model for infection biology and antimicrobial resistance research
Image Credit: Courtesy of University of Exeter
Scientific Frontline: "At a Glance" Summary
- Main Discovery: Scientists at the University of Exeter have developed the world's first genetically engineered greater wax moths (Galleria mellonella) to serve as advanced alternatives to rodents in infection research.
- Methodology: The research team adapted genetic tools originally designed for fruit flies, utilizing PiggyBac mediated transgenesis and CRISPR/Cas9 knockout techniques to create fluorescent and gene-edited moth lines.
- Key Data: Replacing just 10% of UK infection biology studies with these engineered moths would spare approximately 10,000 mice annually from the estimated 100,000 currently utilized.
- Significance: This development addresses the critical bottleneck in antimicrobial resistance (AMR) testing by providing a scalable, ethical non-mammalian model that survives at human body temperature (37°C) and mimics mammalian immune responses.
- Future Application: The creation of "sensor moths" that fluoresce upon infection or antibiotic contact will allow for real-time, visual monitoring of disease processes and rapid drug screening.
- Branch of Science: Biotechnology and Infection Biology
- Additional Detail: All developed protocols and genetic resources have been made openly available through the Galleria Mellonella Research Center to accelerate global standardization and adoption.
A scientific breakthrough not only promises faster testing for antimicrobial resistance, but also an ethical solution to the controversial issue of using rodents in research.
University of Exeter scientists have created the world’s first genetically engineered wax moths – a development which could both accelerate the fight against antimicrobial resistance (AMR) and significantly reduce the need for mice and rats in infection research.
The study, published in Nature Lab Animal, outlines how Exeter researchers have developed powerful new genetic tools for the greater wax moth (Galleria Mellonella). This small insect is increasingly recognized as a cost-effective, ethically sustainable alternative to mammals.
Dr James Pearce from the University of Exeter said: “With AMR posing one of the biggest threats to human health, we urgently need faster, ethical, and scalable ways to test new research. Engineered wax moths offer exactly that – a practical alternative that reduces mammalian use and accelerates knowledge discovery.”
Unlike most other non-rodent model organisms, the greater wax moth can be reared at 37 degrees Celsius – human body temperature – and the response of its cells to bacterial or fungal infection closely mirrors that of mammals. Yet, until now, its use as a model organism has been limited by the lack of genetic tools. Exeter researchers have overcome this by adapting technologies originally developed for fruit fly research, to create fluorescent transgenic and gene edited moth lines for the first time.
Professor James Wakefield from the University of Exeter said: “By putting new genes into the wax moth genome, we’re able to make larvae that glow in a controlled way. This paves the way for ‘sensor moths’ that light up when infected or responding to antibiotics – offering a living, real-time window into disease.”
Sensor moths could transform early-stage infection studies, enabling rapid antimicrobial screening and immune response analysis in a whole organism, without the need for mice or rats. The larvae respond to human pathogens such as the superbug Staphylococcus aureus or the opportunistic fungus, Candida albicans, and therefore provide a realistic yet ethical bridge between cell culture and animal testing.
Dr. James Pearce continued: “Our methods make wax moths genetically tractable for the first time. The ability to insert, delete or modify genes opens huge potential, from understanding innate immunity to developing real-time biosensors for infection.”
The impact on the use of animals for scientific experimentation could be substantial. Each year, around 100,000 mice are used in the UK for infection biology research. If only 10 percent of those studies were replaced with moths, over 10,000 mice annually could be spared – while still generating robust, human-relevant data.
Funding: This research builds on over five years of investment from the National Center for the Replacement, Refinement and Reduction of Animals in Research, alongside collaboration and funding from the Defense Science and Technology Laboratory, and the University of Exeter’s advanced imaging and genomics facilities.
Published in journal: Nature Lab Animal
Title: PiggyBac-mediated transgenesis and CRISPR–Cas9 knockout in the greater wax moth, Galleria mellonella
Authors: James C. Pearce, Jennie S. Campbell, Joann L. Prior, Richard W. Titball, and James G. Wakefield
Source/Credit: University of Exeter | Tom Seymour
Reference Number: btech021026_01