RNA - Genetherapys
Spoke 1 - Genetic Diseases


Spoke 1 aims to foster innovation that accelerates translational research from “bench to bedside” by developing gene therapies and RNA therapeutics to treat a select group of incurable genetic diseases. Spoke 1 focuses on specific organ systems and disease-oriented Work Packages (WPs). Key activities are framed behind defining early lead candidates (Technology Readiness Level, TRL, 1-2), demonstrating preclinical proof of concept (TRL 3-5), and implementing phase I and phase II of clinical trials (TLR 6-9).

Specific research programs define each of Spoke 1 WPs.
WP 1.1 SKIN – Epithelial stem cell-based gene therapy (GT) for genetic skin diseases such as Epidermolysis bullosa and Lamellar ichthyosis.
WP 1.2 BLOOD – GT and RNA therapy (RT) for blood-related genetic diseases, including Sickle Cell disease, thalassemia, hemochromatosis, Ferroportin Disease, Hemophilia A, and rare red blood cell diseases.WP 1.3 EYE – Corneal stem cell applications, gene editing (GE), and microRNA therapy for genetic eye diseases like Meesmann corneal dystrophy, inherited retinal degeneration, and optic neuropathies.
WP 1.4 STORAGE DISEASES – Hematopoietic stem cell-based GT and RT for genetic storage diseases such as Lipofuscinosis 1, neuropathic storage diseases, mucopolysaccharidosis type VI, and Pompe Disease.
WP 1.5 KIDNEY – RT and GE therapy for genetic kidney diseases including Birt-Hogg-Dubé (BHD) syndrome, Tuberous sclerosis complex (TSC), and Alport syndrome.
WP 1.6 NEUROMUSCULAR AND NEUROMETABOLIC DISORDERS – RT, GE, and GT targeting mitochondrial, neurometabolic, neurodevelopmental, and neuromuscular diseases, such as Friedreich’s ataxia, mitochondrial diseases of nuclear origin, Duchenne muscular dystrophy, Rett syndrome, PRUNE_1disease, and Central core disease.



Aimed at creating a state-of-the-art research center, Spoke 1 is dedicated to the study of genetic diseases (in particular, liver diseases) using 3D culture and organoid technology. Participation in the National Center represents a significant leap forward in our ability to understand, treat, and ultimately cure rare, severe, and often incurable disorders. Based on isolated pluripotent or adult stem cells that self-assemble in complex 3D structures, organoids have emerged as an innovative model system that is remarkably similar to actual human organs, thus making the study of biological processes in a physiological and animal-free setup feasible. Traditional 2D cell cultures and animal models often fail to replicate the complexities of human disease. Cutting-edge 3D culture and Organoid systems overcome these limitations by offering a more accurate and ethical alternative for studying human liver diseases and testing potential treatments. National Center activities consist of bio-assembling 3D functional organ-like structures from patient-derived tissues and/or from genetically engineered human-induced progenitor stem cells that closely mimic human organs (such as the liver), providing an unparalleled platform for understanding genetic diseases and testing new drugs. Laboratories will be equipped with the latest cell culture technology, imaging systems, molecular biology tools, and high-throughput screening facilities to foster groundbreaking research.


Active collaborations and coordinated efforts are underway with both horizontal and vertical spokes. Spoke 3 will focus on neurodegenerative, neurodevelopmental, and neuromuscular disorders. Spoke 6 will aim at the development of RNA tools and strategies.
Spoke 7 focuses on the implementation and optimization of biocomputing strategies. Spoke 8 seeks to exploit delivering/targeting approaches, while Spoke 10 is devoted to the sharing of protocols and medicinal products.
Spoke 1 affiliates also include the Chiesi Group, a prominent Italian pharmaceutical company with a mission to identify new and advanced therapies for rare diseases. The Chiesi Group actively engages as a partner by significantly contributing to specific projects within Spoke 1.