| Posted: Feb 04, 2018 |
Modular DNA nanoswitches get close and light up specific biomarkers
(Nanowerk News) Biomolecules are like humans: they can physically interact only when they are in close proximity. However, the crowded environment of a cell resembles what happens in a big metropolis where casual encounters are virtually impossible. Just like humans, biomolecules need common friends and places to get close and interact. Mother Nature invented many strategies to bring biomolecules closer so that they can meet and interact and these mechanisms are at the basis of life. For example different cell receptors can catch biomolecules and bring them closer in cell environment so that they can finally meet and interact.
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In a recent paper published in the Journal of the American Chemical Society ("Programmable Nucleic Acid Nanoswitches for the Rapid, Single-Step Detection of Antibodies in Bodily Fluids") researchers of the University of Rome, Tor Vergata in collaboration with the start-up company Ulisse BioMed and researchers from the University of Brescia have demonstrated that this mechanism can be recreated in a lab to detect biomarkers in clinical samples.
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Video shows an artistic rendering of the nanoswitches in action when bound to the target antibody. (Video: Laboratory of Biosensors and Nanomachines, University of Rome Tor Vergata)
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The researchers have designed and engineered hybrid molecular nanoswitches made of synthetic DNA, peptide-nucleic acid and amino acid residues that, through a specific recognition element, are able to bind target analytes (antibodies) and consequently emit a fluorescent signal. The nanoswitch is composed of two modules, a Reporter module and an Activating module that light up only when they interact with each other, but this is virtually impossible as their concentration in the sample solution is very low and casual encounters are extremely difficult. However, if a target biomarker (i.e. antibody) is present in the sample, it will bind the two nanoswitch modules decreasing dramatically their distance and bringing them in close proximity. The modules can now finally interact and give a fluorescent output that signals the presence of the biomarker in the sample.
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The researchers demonstrated that it is possible to use such nanoswitches to detect a wide range of target analytes (by simply changing the recognition element attached to the switches). An interesting application they poved possible is immunotherapy real-time monitoring. Scientists were able to measure the amount of antibodies raised up following an anti-HIV immuno-therapy which has been used in a clinical trial by Professor Arnaldo Caruso (University of Brescia), co-author of the paper. This platform could thus help to monitor the efficacy of immunotherapies, vaccines and drugs opening new scenarios in the field of personalized medicine, as well as in the field of rapid and cost-effective diagnostics applications, through the instantaneous detection of clinically relevant biomarkers related to pathogens and tumors.
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“The approach we propose is extremely innovative and presents several advantages compared to current methods used to detect antibodies” said Prof. Francesco Ricci of the University of Rome Tor Vergata and senior author in the paper. “The nanoswitches we have developed with Ulisse BioMed give a response within a few seconds, they are very sensitive and have a cost that is about 10-fold lower when compared to the current commercial methods”.
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Dr. Alessandro Porchetta, researcher at the University of Rome Tor Vergata and co-first author in the paper points out other advantages of the system: “The method we have developed utilizes synthetic DNA to design the nanoscale switches that signal the presence of biomarkers. Synthetic DNA is a very versatile material because we can attach to it different molecules that can provide recognition to different clinical targets (not just antibodies!). We are now working on adapting the platform to electrochemical detection that will enable us to miniaturize diagnostic devices thus creating small point of care devices that are accessible, fast, affordable and sensitive”.
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“The future of this type of diagnostic platform is bright” says Dr. Rudy Ippodrino, co-first author of the paper and Chief Scientific Officer of the young Italian start-up company Ulisse-BioMed. “we are currently working on adapting this platform for many different targets so that it can be used for the Diagnostics, Theranostics and Vaccine Monitoring. Our aim is a portable diagnostic device (much like a glucometer) that is capable of detecting infections, cancer, and of monitoring vaccine efficacy and drug levels in the blood”.
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