Fascinating, useful nucleic acids

Nucleic acids are wonder molecules: from their central role in the origins, evolution and architecture of life, to their endless secrets hidden in our genomes, to their incredible structural and chemical versatility, which make them precious tools in several applications. Here I will present some of my works using nucleic acids in diagnostics and therapeutics applications. In particular, I have used nucleic acids functionalized metal nanoparticles to develop rapid diagnostics tests with a naked-eye colorimetric detection. By exploiting the optical properties of metal nanoparticles, their ability to act as nanozymes and optimized assay design via cooperative hybridization of oligonucleotides, I realized prototypes for the analysis of complex real world samples, with a focus on sensitivity, specificity and robustness. Such tests are the subject of 6 granted patents and an award-winning spin-off project, Nanochrome. Examples include tests for the analysis of rare point mutations in circulating tumour DNA, for the genetic fingerprinting of food, and for the detection of nuclease contaminants. More recently, I focused on the design of novel RNA therapeutics, in particular studying a class of non-coding RNAs (ncRNAs) therapeutics, which act through their functional 3D structure, rather than by mere hybridization with the target. I characterized the set of post-transcriptional modifications and the structural requirements needed for activity, resulting in the identification of a core functional structure.
These aspects are essential to design in vitro transcribed ncRNAs with optimal activity, stability, cellular uptake and correct subcellular localization. Once again, nature offers not just the information encoded by the sequence, but a functional folding and added chemical moieties, which add novel properties and potentialities, useful for the design of therapeutics. Aside from providing tools for novel functionalities, nature has already solved also the issue of delivery, as RNA is naturally transferred through inter-cellular, inter-species, and cross-kingdom routes. I am thus also studying how exogenous RNA is trafficked in microbiome-host interactions, in order to develop new microbiome-based RNA therapeutics.

References
Valentini P et al., Molecular Therapy-Nucleic Acids 2022, 27, 1092
Udayan G, Marsella A and Valentini P.*, Nanoscale 2020, 12, 2973
Bertolacci L*, P. Valentini#, and P.P. Pompa#*, Scientific Reports 2020, 10, 18340
Valentini P et al., Angewandte Chemie 2017, 56, 8094
Valentini P et al., Angewandte Chemie 2016, 55, 2157
Valentini P et al., Nanoscale 2016, 8, 11027
Valentini P et al., ACS Nano 2013, 7, 5530