RNA - Genetherapys
Spoke 10 - Pre-clinical Development, GMP Manufacturing and Clinical Trials of GTMP


Academia faces a significant hurdle in progressing Gene Therapy Medicinal Products (GTMP) projects toward a clinical application due to the relevant financial, technical, and logistical challenges associated with the process development, scale-up, and manufacturing under the current Good Manufacturing Practice (cGMP). This often leads to the discontinuation of products despite initial proof-of-principle, which results in high costs and prolonged delays for the few projects that do persevere.

Spoke 10 aims to overcome this challenge by capitalizing on the widely recognized scientific and technical expertise within its membership. The goal is to enhance and fully optimize the translation of cutting-edge pre-clinical research into clinical trials for novel GTMPs. To accomplish this objective, Spoke 10 will implement several pilot training projects, chosen strategically for their exemplary significance. Spoke 10 will develop and lead the early clinical testing of innovative chimeric antigen receptor (CAR)-based approaches. Such testing will tackle some of the most clinically relevant unmet medical needs in pediatric hematology/oncology, including T-cell acute lymphoblastic leukemia (T-ALL), B-ALL relapsing after allogeneic stem cell transplantation, acute myeloid leukemia (AML), brain tumors, and severe B-cell mediated autoimmune diseases. Spoke 10 will develop cutting-edge gene therapies to provide a definitive cure to genetic disorders, such as thalassemia, lysosomal storage disorders with bone involvement, metachromatic leukodystrophy, and Stargardt disease. Each of these pilot projects will specifically target key obstacles faced in the field, which aim to demonstrate potential solutions and to facilitate the advancement of GTMPs from pre-clinical research to clinical trials.

Researcher will make use of existing facilities, which will undergo further enhancements and scaling-up to align with the National Center mission. Following an initial phase focused on training and enabling, Research results will be poised to accommodate projects from other Italian Academic Institutions. Additionally, Spoke 10 is deeply committed to establishing and strengthening mutually beneficial collaborations with pharmaceutical and life science biocompanies, including Takis Biotech, IRBM Research Group, InnovaVector, and Performing Beyond Limits (PBL Srl). The companies affiliated to the Spoke will substantially contribute to the activities that will be pursued by the Spoke 10, facilitating the transferability of research results to industry, increasing the value of the intellectual properties (IPs) owned by Italian research centers through the out-licensing of more mature technologies.

These perspectives, coupled with the training of a new generation of scientists, biotechnologists, clinicians, and experts in emerging techniques, will advance Italy’s biotechnology level to attract investors and developers from abroad.

dna structure spoke 10


Each participant possesses the necessary equipment to execute the proposed tasks, and Spoke 10 will harness their synergy across each Work Package (WP). Additionally, Spoke 10 ambitiously intends to adapt existing infrastructures to international standards (Spoke flagships).
The refurbishing of the GMP facility of Ospedale Pediatrico Bambino Gesù (OPBG)/Fondazione Tettamanti will increase its capability. This scale-up of GMP-compatible processes will ensure that innovative drug products can be tested for early-stage clinical trials.


The strong collaborative efforts of Spoke 7 will provide the development of a comprehensive bioinformatics environment for omics data analysis when cloning vector-transduced cell populations. This work aims to monitor the fate of individual gene-corrected cells in vivo, assess vector integration and, thus, biosafety. The generated drug predictions based on Computational Systems Biology and integrative data analysis offered by Spoke 7 will provide Spoke 10 activities with the computational tools needed to discover novel targets and develop immunotherapeutic approaches.

Spoke 10 expertise and infrastructures will be available across the National Center for Gene Therapy and Drugs based on RNA Technology for the development of clinical grade GTMPs for all Vertical Spokes (1-5).