Multifunctional Peptide Nucleic Acids (PNAs) as smart components for biomedical and technological applications

PI:

Michele Saviano

Email:

michele.saviano@cnr.it

Affiliation:

Dipartimento di Scienze e Tecnologie 
Ambientali, Biologiche e Farmaceutiche (DiSTABiF) 
Università degli Studi 
della Campania "Luigi Vanvitelli"

ORCID:

0000-0001-5086-2459

Peptide Nucleic Acids are one of the best-performing chemical tools for DNA/RNA recognition and manipulation. PNA properties can be changed using chemical modification, thus regulating affinity and selectivity for DNA, inserting reporter groups, regulating cellular uptake. The combination of PNAs with nanostructured materials can lead to several important applications, not only for overcoming the intrinsic PNA poor solubility and low cellular uptake, but also to use the PNA code for programming functions and self-assembly. Aim of the present project is to obtain new PNA structures and PNA-containing nanosystems enabling to combine DNA/RNA binding with one or multiple other functions that can be programmed by design, leading to new biological applications. To achieve these goals, a fundamental research will be carried out, starting from the very basic properties of PNAs and from the nature of their interactions with DNA, RNA, proteins and other biological macromolecules.

The project will include STRUCTURAL AND MODELLING STUDIES, SYNTHESIS OF PNAs AND MODIFIED PNAs, PNA-BASED ACTIVE MULTIFUNCTIONAL NANOMATERIALS, BIOLOGICAL STUDIES IN CELLS ABLE TO RICAPITULATE CANCER MICROENVIRONMENT, and PNA-BASED DIAGNOSTICS.

This project fits one of the missions of the new European Framework Programme “Horizon Europe”, that recognizes cancer as a major issue in society today, and the European Commission’s Innovative Health Initiative (IHI) promoting the integration of cross-sectoral technologies, and multidisciplinary approach to fight cancer. The long-standing idea that nucleic acid-based therapeutic could pave the way for rationally-designed treatments has gained great momentum in recent years, with the advent of marketed antisense drugs (e.g. Kynamro and Exondis), siRNA treatments (Onpattro), and the strikingly successful mRNA technology that allowed to obtain vaccines for COVID-19 (2020). MiR-based and anti-miR drugs are in the pipeline to become new drugs. As far as clinical trials (www.clinicaltrials.gov), an example of anti-miRNA therapeutics is a Phase I trial based on targeting miR-122 for therapy of HCV-infection. Most importantly, the vector technology that allows to deliver nucleic acids and their analogs to cells, has become the winning ace for reaching these important goals. The PNA technology has all the characteristics to be part of this wave of next-generation (or ‘precision’ personalized) medicine, not only as active ingredients targeting important functional genes and non coding-RNAs, but also as components for obtaining more effective and controllable materials that will allow targeted delivery and co-delivery of different drugs. In this context, the project has the aim to strengthen the recognized positioning of Italian research in this strategic field, gathering researchers that have the expertise to improve the performances of PNAs and of PNA-containing nanomaterials, to develop new rationally designed multifunctional nanosystems, and to use PNA in new biological applications.

Figure Legend: PNA synthesis at the automated parallel synthesizer
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