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.

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.

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.

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.

References

1. Gootenberg, J. S., et al. (2017). "Nucleic acid detection with CRISPR-Cas13a/C2c2." Science 356(6336): 438-442.
2. St John, A. and C. P. Price (2014). "Existing and Emerging Technologies for Point-of-Care Testing." Clin Biochem Rev 35(3): 155-167.
3. 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.
4. 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.