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Descrizione del progetto

The platforms that will be developed with the present research project will be able to simultaneously bind NAs and specific receptors present on the cells of targeted diseases, being able to fulfil the requirements of the Call and the Track A1. The modularity with whom they have been designed makes them universal and personalized. Universal since they can bind to NAs of different type and length (DNA, miRNA, premiRNA and most probably also mRNA). Interestingly, these are among the sole molecular delivery systems able to internalize PNA inside cell, being this type of artificial NAs quite peculiar due to their neutral skeleton. This class of platforms will also be personalized since by simple and efficient protocols they could be modified to graft onto their structure several proper targeting ligands, spanning from peptides, carbohydrates, steroids and potentially even aptamers, at will, and depending on the type of cell to be addressed. The prototype of this polycationic platforms, lacking the targeting units, and thus having no specificity for any cell line, have reached TRL 4. A priori, the insertion of the targeting units might (partially) impair the ability of the platforms to bind, deliver or release its NA cargo. If we will observe any of these drawbacks, as a risk mitigation measure, we can modify the position of grafting the targeting units on the platforms, having the three different alternatives depicted in figure 2 A, B, C, or even move to a noncovalent approach where we will a distinct selector and vector platforms already consolidated in carrying out their task (select the receptor and deliver the NA). After having defined the proper functionalization methodologies, we will then prepare a series of platforms bearing peptides and carbohydrates indicated in WP1 that will enter the Spoke #8 high-throughput discovery pipeline and the subsequent selection of candidates to demonstrate the PoC that is possible to produce smart platforms for the precision NA delivery. We therefore think that thanks to the cooperation with the research groups present in the Spoke #8 and potentially in the other Spokes, at the end of the programme these novel platforms for the precision delivery of NAs might potentially even reach TRL 7. The modularity of our approach aiming at grafting the targeting unit to a preformed polycationic platform by using user-friendly procedures will also allow to transfer these preparation procedures to biology/biotechnology or even medicine laboratories that would need to click their own ligands on the platform, and thus obtaining personalized vectors for NATs.

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