Mission

• The Foundation known as the National Research Center "Development of Gene Therapy and RNA-Based Drug Technology" conducts research in areas of strategic importance for the country for the production of therapies or the design of procedures for human health, integrating therapy development with precision delivery.

• Its goal is to create and renovate research infrastructure and laboratories, as well as to implement and develop research programs and activities to foster the emergence and growth of high-tech entrepreneurial initiatives (innovative start-ups and research spin-offs), aiming to capitalize on research results in the specified fields.

Objectives

• To develop a novel generation of delivery technologies and speed up the translation of therapeutic concepts proposed in CN-3 vertical spokes in pharmaceutical products with an unprecedented interdisciplinary effort, merging chemistry, nanotechnology and pharmaceutical technology, imaging and microscopy, bioengineering, molecular biology and pharmacology.

• To advance knowledge in pharmaceutical nanotechnologies through the discovery of novel functional materials, strategies of nanoparticle engineering toward precision delivery and the development of human-relevant models to assess the efficiency of delivery

Open issues

• Lack of efficient delivery technologies that allow the therapeutic cargo to reach the cellular target
• Delivery of nucleic acids to extrahepatic sites is in its infancy and requires novel solutions (precision delivery)
• Precision delivery is operated in a poorly translational perspective generally moving from technology to patient rather than the opposite
• Poor availability of robust pre-clinical models for the early assessment of the delivery efficiency
• Nanotechnology based solutions do not often translate into a product due to a lack of stability or quality
• Requirements
• Technologies for the gram scale production of different types of nanoplatforms need to be extended

Spoke 8 - Platforms for RNA/DNA Delivery

The primary goal of Spoke 8 is to pioneer a new era of drug delivery technologies and expedite the transformation of theoretical therapeutic concepts from vertical Spokes into tangible pharmaceutical products. Central to this objective is the advancement of knowledge in pharmaceutical nanotechnologies.

This includes exploring innovative functional materials, developing strategies for engineering nanoparticles for precise delivery into the body, creating human-relevant models for assessing delivery efficiency, and developing novel manufacturing technologies.

DIFARMA

Within the CN3 National Research Center, DIFARMA’s activities are integrated into Spoke 8: Platforms for RNA/DNA Delivery. Specifically, in Work Package 8.2: Human relevant models to assess delivery efficiency, DIFARMA serves as the task leader for Subtask 8.2.3: High-throughput analysis linking in vitro models and disease features.

The subtask's objective is to provide insights into the efficacy, toxicity, and safety of new RNA formulations by studying molecular-level events in both traditional in vitro systems (cell cultures) and innovative models such as organoids. Specifically, for Subtask 8.2.3, the activities focused on employing multi-omics approaches, driven by mass spectrometry, for characterizing patient-derived organoids (PDOs) of colorectal cancer (CRC). The methodologies developed enable single-analysis characterization of the proteome, metabolome, and lipidome of the organoids following treatment, aiming to elucidate the mechanisms underlying drug interaction.

Additionally, DIFARMA is involved in Work Package 8.1: Translational development of smart delivery platforms, particularly in Subtask 8.1.2: Multifunctional synthetic nanoplatforms for precision delivery. This subtask targets the design and optimization of polysaccharide-based nanoparticles for oral or localized delivery of siRNA in the treatment of colorectal cancer.