Antimicrobial resistance (AMR) is one of the most pressing public health threats of our time. As pathogens become resistant to existing treatments, our defences are collapsing, leaving infections that were once curable to spiral out of control. In 2021, an estimated 4.71 million deaths were associated with bacterial AMR, including 1.14 million directly attributable deaths.
Without urgent intervention, this burden will escalate dramatically. By 2050, forecasts indicate AMR could cause 1.91 million attributable deaths and 8.22 million associated deaths annually, with projections suggesting a cumulative toll of up to 40 million lives lost.
The Diagnostic Front
Current gold-standards such as PCR and lateral flow tests suffer from low throughput, limited detection range, or reliance on sophisticated equipment. We have engineered a device that exploits a novel two-step reaction, coupling the identification of pathogenic markers to a simple, visible colour change for accessible, point-of-care diagnosis.
The Therapeutic Front
Available solutions either create pathways for resistance escape or are too limited in their applicability. CASPER re-imagines the therapeutic approach by deploying a cell-based programmable DNA therapeutic agent—the pCASPER plasmid—designed for precise, genetic-level pathogen elimination, minimizing off-target effects.
Explore the CASPER Products
Click the product image above to view the project's high-level description.
Programmable DNA Agents
The core of our therapeutic is the pCASPER plasmid. This engineered DNA agent is delivered to bacterial populations and is programmed to detect specific, unique sequences found only in pathogenic bacteria, utilizing the CRISPR protein Cas12a. Upon recognition, Cas12a introduces a double-stranded break, leading to cell death. This ensures strain-specific killing, sparing beneficial host microbiome.
Advanced Stability and Efficacy
To overcome bacterial defense mechanisms and DNA repair, pCASPER incorporates several advanced features: DNA-repair inhibitors to prevent damage fixation, an Anti-defence island to inhibit bacterial defenses against the plasmid, and two broad-range replication origins to ensure stable replication across various bacterial hosts.
Education
Developing accessible resources and workshops to share synthetic biology with the public and future scientists, ensuring global scientific engagement.
Hardware
Designing and prototyping low-cost, open-source devices for running our diagnostic and therapeutic protocols in field and point-of-care settings.
Software
Creating robust computational models and bioinformatic tools to validate genetic circuits and optimize therapeutic and diagnostic effectiveness.
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Dec 2024: Team assembled and project direction set.
The official Oxford iGEM 2025 team was formed, immediately pivoting to intense debates on project direction, ultimately choosing the high-impact AMR challenge.
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Jan 2025: CRISPR-based focus confirmed.
After exploring various synthetic biology concepts, the team consolidated on using advanced CRISPR technology for both diagnostic and antimicrobial applications.
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Apr 2025: CRISPR targeting algorithm introduced.
Developed a proprietary bioinformatic tool to optimize guide RNA design, maximizing the therapeutic system's precision and reducing off-target effects.
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Jul 2025: pCASPER backbone validated and key collaboration established.
The foundational structure of the therapeutic plasmid was successfully validated, followed by a key collaboration with the Baker Lab to refine protocols.
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Aug 2025: Diagnostic chip re-designed to radial microfluidics.
The diagnostic device was iterated, moving from a standard lateral flow design to a high-efficiency radial microfluidics platform for better fluid control and reliability.
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Sep 2025: BioXchange Conference and diagnostics final verification completed.
The successful hosting of the BioXchange conference coincided with the final verification of the integrated CRISPR-lateral-flow diagnostics system design.
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Oct 2025: Delivery mechanism characterisation finalized.
Final experimental data gathered on delivery systems (EVs/Minicells) confirmed successful transfer of the therapeutic agents into target bacteria.
Operating Principle
Our diagnostic kits rely on the two-step Cas12a collateral cleavage reaction. We immobilize the Cas12a complex on nitrocellulose paper. The reaction is initiated by applying the sample, which, if pathogenic DNA is present, activates the Cas12a. This, in turn, frees the $\beta$-lactamase enzyme to hydrolyse the chromogenic substrate nitrocefin, providing a visible yellow-to-red readout in minutes.
Microfluidics-Assisted 'Box' Design
To improve speed and reliability beyond passive paper-based systems, we developed the 'Box' design, which uses a syringe pump system to actively propel liquids. This preserves the key benefits of microfluidics – high throughput and compact form – while accelerating the overall workflow and improving control over reaction dynamics.
Precision in Design
Our engineering foundation is built on three core pillars: modularity, precision, and efficiency. We utilize established BioBricks and rigorously designed genetic circuits to ensure predictable behavior, minimize metabolic load on the host cell, and maximize the therapeutic or diagnostic output.
The final system incorporates genetic switches tuned for specific host conditions, such as high concentrations of bacterial metabolites or low pH, offering an unprecedented level of control. This careful design is essential for transitioning synthetic biology tools from the lab bench to reliable, real-world clinical applications. Click the image to learn more!
With Sincere Thanks to Our Supporters
Our ambitious project is made possible by the generous contributions of visionary institutions and passionate individuals. We are immensely grateful for their belief in our work.
