A novel approach to analysing DNA for signs of mutation and disease is leading to highly accurate tests for early-stage cancer, antibiotic resistance and genetic disorders, potentially revolutionising diagnostic medicine and saving lives.
© NanoBioPhotonix Lab, TAU
The technology, the result of ongoing research in the EU-funded BeyondSeq project, could be commercialised and ready for use by doctors within a few years, with diagnostic hardware for clinical devices already under development.
We are tapping into innovations in optical mapping, genetic analysis and detection technologies and applying them in a way that has not been tried before for medical diagnosis, explains Yuval Ebenstein, principal investigator at the NanoBioPhotonix Lab of Tel Aviv University, which is coordinating BeyondSeq. Trials conducted so far suggest that the approach results in diagnostic tests that are orders of magnitude more sensitive than current diagnostic tools, particularly for some forms of cancer that are especially hard to detect at an early stage.
Compared to current genetic and epigenetic diagnostic tools, such as DNA sequencing based tests that look for biological markers of mutation and disease across a batch of DNA molecules, the BeyondSeq technology is capable of detecting biomarkers in individual DNA molecules.
With single-molecule detection it is possible to identify a genetic or chemical alteration in each individual cell one-by-one, even in a large blood or tissue sample, long before it could be detected with current diagnostic tools, Ebenstein explains.
Within the BeyondSeq consortium various teams in Europe and Israel are exploring different potential applications for the groundbreaking technology, including diagnosing inherited genetic disorders such as spinal muscular atrophy (SMA), analysing bacteria for antibiotic resistance and developing diagnostic tests for colorectal, lung and blood cancers.
Early detection of colorectal and lung cancer saves lives
Early-stage diagnosis of hard-to-detect cancers is among the most promising applications for the technology. Currently colorectal cancer and lung cancer is often diagnosed late, frequently when multiple secondary tumours have already developed, complicating treatment and reducing a patients chance of survival.
Within the BeyondSeq project, a team at the Technion Institute in Israel is using single-molecule analysis based on nanopore scanners to identify slight variations in specific nucleotides, the building blocks of DNA.
The nanopore scanning technology detects optical and electrical signals from individual DNA molecules, providing information on their length and sequence variations. These signals can be used to identify alterations, such as variations in the DNA nucleotides of the KRAS gene, which have been identified as biomarkers for colorectal and lung cancers.
The BeyondSeq partners, who plan to patent the technology, are currently working on the development of a screening device that could be used in a clinical setting to test patients for key cancer biomarkers.
Meanwhile, a team at project partner Gothenburg University in Sweden is using similar technology to analyse bacteria for signs of antibiotic resistance. The research is set to contribute to a next-generation database that could help refine antibiotic therapies and counter the growing global problem of antibiotic-resistant bacteria, among other applications.
We have taken an unusual approach to developing this technology, setting up different research teams and focusing on testing different applications to determine which are likely to be most effective and have the greatest impact in practice, Ebenstein says. This has led to some very successful results and technologies we should be able to commercialise in a matter of years that are already attracting interest from investors and companies in the healthcare sector.