Periodic Reporting for period 1 - AB-SWITCH (Evaluation of commercial potential of a low-cost kit based on DNA-nanoswitches for the single-step measurement of diagnostic antibodies)
Reporting period: 2017-02-01 to 2018-07-31
The goal of the Ab-switch project was to evaluate the commercial potential of a novel platform for the point-of-care detection of diagnostic antibodies based on the use of synthetic DNA sequences that we have developed and optimized during the ERC Starting Grant project “Nature Nanodevices”. Our approach was initially based on a modular nanodevice (that we named Ab-switch) composed of synthetic DNA. In the initial part of the project, we fully characterized the Ab-switch platform in terms of all the main analytical parameters. We started performing a calibration curve using commercially available anti-HIV antibodies and we achieved a low nanomolar detection limit of the platform for the specific target. In the initial phase of the project we also started contacting In-vitro Diagnostic companies to evaluate possible commercial or R&D agreement. This was made possible also thanks to the fact that in 2017 prof. Francesco Ricci was awarded the prestigious Heinrich Emanuel Merck Award. Since 1988, the Heinrich Emanuel Merck Award has been recognizing scientists under the age of 45 whose work focuses on new methods in chemical analysis and the development thereof in applications aimed at improving the quality of human life, for example in fields such as life science, environmental protection and the biosciences.
Unfortunately, during the meetings we had with companies two problems related to the use of our platform for diagnostic application were identified. The first problem is related to the detection limit achievable with our platform which is currently not low enough to allow the use of this platform for diagnostic applications in HIV patients especially if real samples (whole blood) should be used. The second problem is more technological and regards the use of double modified DNA sequences that might pose problem from a synthetic point of view. For this reason during the course of the Proof of Concept grant we discussed these issues with a start-up company particularly interested in our technology and concluded that two solutions can be envisioned for these problems while still keeping the same positive features of our analytical platform: focusing on a different clinical target (immunotherapy monitoring) and changing the sensing principle. To do so, we coupled the advantages of target binding induced co-localization and nucleic acid nanoswitches. We propose a platform for the detection of specific antibodies in which toehold-mediated strand displacement reaction (TMSD) is employed. We have demonstrated the positive features of this new sensing technology and we are now moving to the detection of a model immunotherapy target: Trastuzumab, a monoclonal antibody sold under the brand name Herceptin, which is currently used to treat breast cancer. This would be a perfect demonstration of the potentials of our technology to possible investors. Considering the change of focus of our new technology we are discussing the possible IP strategy for patent filing with the administration of our University and also with our contacts in the two companies with which we had previous contacts.
Unfortunately, during the meetings we had with companies two problems related to the use of our platform for diagnostic application were identified. The first problem is related to the detection limit achievable with our platform which is currently not low enough to allow the use of this platform for diagnostic applications in HIV patients especially if real samples (whole blood) should be used. The second problem is more technological and regards the use of double modified DNA sequences that might pose problem from a synthetic point of view. For this reason during the course of the Proof of Concept grant we discussed these issues with a start-up company particularly interested in our technology and concluded that two solutions can be envisioned for these problems while still keeping the same positive features of our analytical platform: focusing on a different clinical target (immunotherapy monitoring) and changing the sensing principle. To do so, we coupled the advantages of target binding induced co-localization and nucleic acid nanoswitches. We propose a platform for the detection of specific antibodies in which toehold-mediated strand displacement reaction (TMSD) is employed. We have demonstrated the positive features of this new sensing technology and we are now moving to the detection of a model immunotherapy target: Trastuzumab, a monoclonal antibody sold under the brand name Herceptin, which is currently used to treat breast cancer. This would be a perfect demonstration of the potentials of our technology to possible investors. Considering the change of focus of our new technology we are discussing the possible IP strategy for patent filing with the administration of our University and also with our contacts in the two companies with which we had previous contacts.