H2020Individual fellowship2021–2023

Entropic DNA Sensors · Entropically programmable DNA-based bioSensors for personalized medicine

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2021-05-01 → 2023-04-30
EU contribution
€183,473
Participants
1
Scheme
MSCA-IF

Lines connect the coordinator with its partners.

Results in brief

Entropically programmable DNA-based bioSensors for personalized medicine

Biosensors have achieved a significant feat in bioanalytical chemistry and translational science: high-frequency, real-time and quantitative measurements of clinically relevant molecules in vitro and in vivo. Despite their advantages, our ability to precisely control and regulate the binding activity of their bioreceptors (i.e., the recognition element) still represents a highly relevant bioengineering challenge and limitation. Indeed, complete control of the binding properties of bioreceptors would allow the design of new biosensors with improved and predictable analytical performance. These improvements in bioreceptor properties have a direct impact and benefit on any biosensing technology, not only the newly developed but also the already established techniques. In fact, this will allow the development of innovative, high performance and programmable biosensors capable of achieving personalized medicine. For example, the high precision of the measurements could allow the tailoring of dietary or drug therapy, improving the clinical treatment of cancer, diabetes and metabolic disorders. In the MSCA action (Entropic DNA Sensors), the experienced researcher (Dr. Andrea Idili) proposed a multidisciplinary, innovative and versatile approach that allowed to fine-tune the activity and the response of synthetic bioreceptors. Specifically, the work has focused on the exploration and characterization of various naturally inspired mechanisms, such as entropic allostery and sequestration, as a novel signal transduction mechanism to improve measurement precision. This has allowed the development of a general bioengineering approach to precisely tune biosensor performance through the rational introduction of intrinsically disordered moieties. Finally, the senior researcher demonstrated the application of these mechanisms in representative biosensors (electrochemical and optical) and their use for real-time, high-precision measurements of clinically relevant molecules to achieve the detection of clinically relevant molecules (i.e., doxorubicin, ATP, vancomycin, and NGAL) directly in complex biological fluids in vitro. To achieve these project goals, Dott. Idili's previous experience in in vivo biosensing and point-of-care (PoC) testing technologies was synergistically combined with the recognized expertise in functional DNA nanotechnology and synthetic biology of Prof. Francesco Ricci at the University of Rome Tor Vergata (UNITOV-Rome, Italy).

Data: CORDIS, © European Union

Project objective

My proposed program consists in a 2-year research activity at the forefront of bioengineering, aiming at the development of Entropically programmable DNA-based bioSensors for high-precision medicine (Entropic DNA Sensors). Biosensors have achieved a significant feat in bioanalytical chemistry and translational science: high-frequency, real-time and quantitative measurements of clinically relevant molecules in vitro, and in vivo. Despite their advantages, our ability to precisely control and regulate the binding activity of their bioreceptors (i.e., the recognition element) still represents a highly relevant bioengineering challenge and limitation. Indeed, the fully control of bioreceptor’s binding properties would allow the design of new biosensors with improved and predictable analytical performance. In Entropic DNA Sensors I propose a multidisciplinary, innovative, and versatile approach based on a purely naturally inspired entropic allostery mechanism which allows to finely tune the activity and the response of synthetic bioreceptors. Specifically, my goal is to further explore our ability to rationally design intrinsically disordered domains into classic DNA-based bioreceptors so as to improve their useful dynamic range. Then, I will adapt these intrinsically disordered bioreceptors into an electrochemical read-out modality that supports the real-time, multi-hour, high-frequency, calibration-free measurements of clinically relevant molecules (i.e., doxorubicin, glucose, phenylalanie) directly in complex biological fluids in vitro. Finally, I will test them in simulated clinical scenarios to demonstrate their ability to reach personalized medicine. To achieve this goal I will leverage my experience in In vivo biosensing and Point-of-care (PoC) testing technologies with the recognized expertise in Functional DNA nanotechnology and Synthetic biology of Prof. Francesco Ricci at University of Rome Tor Vergata (UNITOV-Rome, Italy).

Original text from CORDIS.

Participants

  • UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA · RomaCoordinatorItaly

Links

Data: CORDIS, © European Union