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Applied Design
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Diagnosis of infectious diseases and public health
Traditionally, infectious diseases are diagnosed by cell culture or PCR-based methods. As these techniques require expensive infrastructure, trained personal, and time, the current practice suffers from three main problems. First, diagnosis is not available everywhere, and therefore pathogens are usually detected in central clinics2, rather than at the point-of-care (POC). Second, diagnosis is not accessible to everyone. Especially in developing countries proper medical supply is often lacking, due to the high costs. And third, diagnosis is not available within a few hours, which can lead to negligence of laboratory tests, resulting in premature prescription of antibiotics, the primary reason for the recrudescence of resistant bacteria strains3.
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Current solutions for rapid testing
Most point-of-care tests that are currently established on the market, like pregnancy tests, are based on antibodies targeting certain metabolites4. These tests are therefore restricted to one specific application and require long and expensive design cycles for the development of new tests for other applications or changing pathogen epitopes as in case of endemic virus strains with high mutation rate.
According to our contact person at Médecins Sans Frontières (MSF), already existing low-cost POC-test for infectious diseases are mostly based on antibody-based lateral flow tests such as BIONEXIA® Rota Adeno or SMART™II Cholera O1. Recently, qPCR-based systems were developed that provide a more universal solution for highly automated nucleic-acid detection. According to our contact person at MSF, also cartridge-based systems are currently employed as POC diagnostics for in-field applications. GeneXpert allows the detection of MRSA in patient samples, and Alere™ q provides an automated bench top platform for nucleic acid testing in any healthcare setting.
These qPCR- and ELISA-based methods represent a significant advance in the portability and usability of point-of-care testing. However, these tests include plenty of plastic waste and cost around 10$ for consumables and several thousands of dollars for the main device. This is too high for applications in developing countries for which doctors without borders calls a price of less than 1$ per test.
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CascAID as an ultimate solution
We developed CascAID to combine the portability, affordability, and usability of point-of-care tests with the universality and sensitivity of PCR-based nucleic acid detection. We achieve this by using the tools of synthetic biology to minimize hardware requirements and by supplying CascAID in a low-cost paper-based format.
Due to the rapid, software-aided design of crRNA, CascAID can be easily adapted to a variety of targets - from bacterial infections and rapidly evolving viral epidemics to cancer-associated mutations.
Additionally, the Cas13a enzyme was shown to find targets with a single-nucleotide specificity, superior to PCR-based methods1. CascAID can be entirely conducted on-site by the doctor or patient and therefore reduces the logistic complexity, drastically hastening the diagnostic process.
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Impact on lives
With CascAID we venture to solve global health challenges and therefore impact the lives of people living in the developed world, as well as developing countries.
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Global epidemics
CascAID can be made available everywhere. Due to its small size and little infrastructure requirements, CascAID can be used in mobile health-stations visiting remote areas, lacking a centralized healthcare system. This minimizes the travel expenses of patients living far from hospitals and therefore aids to receive a timely cure. As CascAID can be rapidly customized to fit local variants of pathogens, it is applicable in any region on the globe. By employing it as a safety test at airports, it would assist in containing the spread of potential global epidemics like Ebola, Zika, or the plague.
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At home testing
CascAID is accessible to everyone. Designed with an open-source philosophy, the hardware, like our fluorescence detector Lightbringer, can be assembled from common low-cost components by anyone. We did a poll, to address the question of whether people would use CascAID to diagnose themselves for infectious diseases at home, without going to a doctor. Although we received a good resonance from the public, we think that a universal tool for nucleic acid testing is very powerful and therefore raises ethical issues. If applied for detection of, e.g., severe genetic diseases or HIV, the presence of a doctor is also essential for guidance and psychological aid, which is why usage of such tests must be debated and regulated appropriately. More information on risks of self-tests can be found on our Safety page.
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Antibiotics resistance
CascAID is fast and high-sensitive. This is crucial to enable a timely and appropriate therapy. For instance, the ability to distinguish between viral and bacterial infections would be of great importance for lowering antibiotics over-prescription. This way a misuse of antibiotics as a leading reason for multi-resistant bacteria strains would be significantly reduced.
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Spin-offs
Finally, as CascAID is a modular platform, single parts can be used as a spin-off. For instance, our detector could serve as a tool to measure kinetics of biological or chemical reactions, that is available to other iGEM teams or research laboratories.
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References
- Gootenberg, J. S., et al. (2017). "Nucleic acid detection with CRISPR-Cas13a/C2c2." Science 356(6336): 438-442.
- St John, A. and C. P. Price (2014). "Existing and Emerging Technologies for Point-of-Care Testing." Clin Biochem Rev 35(3): 155-167.
- Llor, C., & Bjerrum, L. (2014). "Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem." Therapeutic Advances in Drug Safety, 5(6), 229–241.
- Peeling, R. W. and R. McNerney (2014). "Emerging technologies in point-of-care molecular diagnostics for resource-limited settings." Expert Rev Mol Diagn 14(5): 525-534.
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