RNA - Genetherapys
Spoke 5 - Inflammatory and Infectious Diseases

PROGRAM

Spoke 5 is organized into four primary Work Packages (WPs), each dedicated to advancing cutting-edge research in the fields of vaccines, therapeutic RNA discovery, innovative infection-fighting strategies, and RNA-based drug design and delivery.
WP 5.1 focuses on developing a versatile platform for viral vaccines, specifically leveraging a “replication-deficient” Sendai virus vector to produce an alternative SARS-CoV-2 vaccine. State-of-the-art technologies will assess the immunogenicity and efficacy of vaccines. Additionally, platforms for generating prophylactic drugs will include mRNA-encoding neutralizing antibodies that are under development. Another facet involves engineering innate immune molecules for therapeutic purposes while addressing viral infections and autoimmune disorders.
WP 5.2 focuses on non-conventional strategies to combat challenging bacterial infections and novel viruses. Specific activities include identifying bacteriophages capable of targeting resistant bacteria, employing Genomics-Informed Drug Design (Gen-ID2) technology, and designing aptamers to target and destroy infected cells. The Gen-ID2 technology aligns with efforts in Spoke 1, offering the potential for personalized cancer treatments with reduced side effects.

WP 5.3 is dedicated to discovering circulating RNAs as biomarkers and therapeutic targets in immune and inflammatory diseases. The focus of WP 5.3 extends to analyzing extracellular vesicle-associated non-coding RNAs as potential biomarkers and targets. Establishing a core facility for high-throughput sequencing analysis, initially focusing on Type 1 Diabetes and pulmonary fibrosis, with potential applications in various diseases across different Spokes.
WP 5.4 centers on designing RNA-based drugs and delivery methodologies. The efforts include reprogramming dendritic cells using RNA to address immune pathologies related to transplantation and autoimmunity and developing a platform for cell-based therapy to control graft-versus-host disease and autoimmune disorders. Additionally, WP 5.4 will explore programmable viral and non-viral lipid-based RNA/DNA delivery systems to enhance therapeutic development and delivery.
These comprehensive research initiatives underscore Spoke 5’s commitment to advancing scientific knowledge, fostering collaboration, and contributing to the development of innovative solutions for infectious and inflammatory diseases.

Spoke 5


SPOKE FLAGSHIPS

Several activities within Spoke 5 receive robust support from small and medium enterprises (SMEs) and pharmaceutical companies.
For Work Package 5.2 (WP 5.2), we capitalize on the innovative Genomics-Informed Drug Design (Gen-ID2) platform (Task 5.2.2), designed to selectively recognize and degrade viral genomic RNA. This platform holds immense potential, offering treatments for diseases influencing the genetic profile of affected tissues, aligning with the objectives of Spoke 1 and Spoke 2. The considerable market size for such treatments is promising. Our collaboration with the American start-up, Entropy Therapeutics, further strengthens this initiative. Entropy Therapeutics, having patented carriers for use in the Genomics-Informed Drug Design (Gen-ID2) platform, has committed to granting the National Center favorable patenting rights and supporting the technology’s application development.
The innovative platform for in vitro transfection of monocytes/dendritic cells with mRNA, aiming to generate tolerogenic cells, has been patented. Its development and translation to the clinical setting are being propelled with the support of BioNTech (Germany).
Spoke 5 has established a core facility dedicated to high-throughput sequencing analysis of circulating RNAs associated with multiple blood plasma components. This facility is pivotal in discovering novel biomarkers for therapy response, enhancing precision medicine approaches, and unveiling innovative therapeutic targets.
This strategic initiative amplifies Spoke 5’s commitment to advancing research and fostering collaborations in the pursuit of breakthrough discoveries.


CROSS-SPOKE ACTIVITIES

Ongoing collaborations and synergized efforts are actively driving our research initiatives. In partnership with Spoke 8, we are undertaking an in-depth analysis and development of extracellular vesicles as potential therapeutic vectors. This involves the targeted delivery of RNA molecules into specific cells of interest, such as insulin-producing beta cells and lung cells. Given the utilization of high-throughput RNA-omics technologies and the anticipated substantial volume of data from various sample sources, Spoke 5 will be closely engaging with the biocomputing infrastructures established in Spoke 7. This collaboration aims to streamline -omics data analysis and facilitate data access for the entire National Center.