MUltifunctional Molecular Platform for NUcleic AcidS Precision Delivery – MUNUS

Funder: Project funded under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.4 – Cascade Call related to the Program “National Center for Gene Therapy and Drugs based on RNA Technology (CN RNA & GENE THERAPY) – Spoke 8” funded by the European Union – NextGenerationEU

Award Number: Cascade Call related to the Program “National Center for Gene Therapy and Drugs based on RNA Technology (CN RNA & GENE THERAPY) – Spoke 8”, CN00000041, CUP [D53C23003990007], IRIS Archive number 78F687889C 

Start date: 25/03/2024

End date: 24/03/2025

Total NRRP funding for the cascade call: € 460.700,00

Total NRRP funding for Unipr: € 460.700,00

Objectives

The National Center focuses on Gene therapy and RNA-based treatments, which represent a groundbreaking approach to healthcare. These personalized interventions leverage an individual’s molecular profile, precisely targeting disease pathways while minimizing effects on normal physiological mechanisms. Their flexibility allows adaptation to changing disease patterns, and their duration can vary from short-term (as seen with mRNA vaccines) to lifelong results through DNA modification. Spoke 8 is dedicated to revolutionizing drug delivery by transforming theoretical health concepts into real-world medications. It emphasizes pharmaceutical nanotechnology, including the creation of new materials, precise nanoparticle engineering, and the development of human-like models for testing delivery effectiveness.

Activities

Nucleic acid-based therapeutics (NATs) hold promise for treating a variety of diseases. However, their delivery is complicated due to factors such as target specificity and stability. The goal of this project is to develop a novel delivery method that does not depend on traditional polymeric or lipid systems. Instead, the new approach involves the use of functionalized targeting units. These units have the ability to bind to the nucleic acid and selectively attach to the host cell. This could potentially enhance the precision of delivery and reduce the entrapment of RNA nanoparticles in organs like the liver and spleen.

The MUNUS project aims to go beyond the current state of the art by proposing novel platforms for the selective targeting of cells and the delivery of NAs and by developing new inhalation formulations for the administration of NAs, specifically designed for the selective treatment of tumours. The objectives of the project are twofold, both aiming at increasing the selectivity in the delivering of NAs: first, to develop macrocycles functionalized with proteins and carbohydrates able to complex and deliver Nas selectively to tumour cells; and second, to insert these structures into an efficient inhalation product (nasal or pulmonary). This project marks a revolutionary advance in the field by combining the cell targeting aspect of nucleic acid delivery with its incorporation into an inhaled medicinal product that delivers NAs to the site of absorption.

• Department of Chemistry, Life Sciences and Environmental Sustainability
• Department of Food and Drug

• Università degli Studi di Parma (UNIPR)

The final target of the Chemistry activities will be: i) definition and synthesis of at least two macrocyclic platforms for precision delivery of NAs with selectivity for their target cells. ii) definition of protocols for the synthesis of macrocyclic platform with reactive groups to be easily grafted with targeting ligands using very simple and fast preparations. iii) scale-up procedures for the production of these platforms. 

The final target of the Pharmaceutical Technology activities will be the achievement of two optimized products, one nasal and one pulmonary, safe, and efficient for the deposition of NAs at the absorption site. A second final target will be to identify the manufacturing conditions capable of maximizing production yields, making the process sustainable and on a large scale for preclinical and clinical batches.

National Center for Gene Therapy and Drugs based on RNA Technology (rna-genetherapy.eu)