Biomolecules are like humans: they can physically interact only when they meet with each other. However, the crowded environment of a cell resembles that of a metropolis where casual encounters are virtually impossible. Just like humans biomolecules need common friends and places to meet and get together.
Nature has invented many strategies to bring biomolecules closer so that they can meet and interact and these mechanisms are the basis for the life as we know it. In cells, for example, different receptors can catch biomolecules and bring them closer in a very small environment where they can finally meet and interact.

In a recent paper published this week in the Journal of the American Chemical Society fruit of a collaborative effort between the University of Rome, Tor Vergata, the University of Udine and the Italian start-up Ulisse-Biomed, researchers have demonstrated that a similar mechanism can be adopted to detect antibodies in clinical samples.
The researchers have designed two synthetic DNA nanoscale switches that can interact with each other and light up giving a measurable optical signal only when they get close to each other. However, because the number of switches in solution is very low it is virtually impossible for them to find each other and interact.

The researchers have thus attached to these two switches a small recognition element that is able to bind to a specific antibody. Antibodies are Y-shaped macromolecules with two sites at the ends of the two arms capable of binding the recognition elements and separated by few nanometers. So, if the antibody is present in solution it will bind the two DNA switches bringing them close together. The DNA switches can now interact with each other and give an optical output. This output can be used to signal the presence of the antibody and its concentration in the sample.

The researchers have demonstrated the possibility to use this strategy to detect a wide range of target antibodies (by simply changing the recognition element attached to the DNA switches). In a very interesting application of this method they have, for example, demonstrated the detection of antibodies that are expressed by HIV patients under immuno-therapy based vaccine treatment currently under clinical trials. This platform could thus help to monitor the efficacy of a treatment or to measure antibodies diagnostic of a specific disease.

“The approach we proposed is extremely innovative and present 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 give a response in few minutes, they are very sensitive and have a cost that is about 10 times lower compared to the current commercial methods used nowadays”.

Dr. Alessandro Porchetta, senior researcher at the University of Rome Tor Vergata and co-first author in the paper point out other advantages of the system: “The method we have developed utilize synthetic DNA to design the nanoscale switches that signal the presence of the antibody. 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!) and also we can use signalling tags that can provide other types of outputs. We are currently investigating for
example the possibility to use electrochemical outputs so that we can further miniaturize and decrease the costs of the platform” concludes dr. Porchetta.