The European Consortium for Communicating Gene and Cell Therapy Information (EuroGCT) unites 49 partner organisations and institutions across Europe, including the major European advanced therapies learned societies, with the common goal of providing reliable and accessible information related to cell and gene therapy development to European stakeholders. EuroGCT has two major objectives: • To provide patients, people affected by conditions, healthcare professionals and citizens with accurate scientific, legal, ethical and societal information and with engagement opportunities, and thus to support better informed decision-making related to cell and gene-based therapies. • To facilitate better decision-making at key points in development of new therapies and thus enable improved product development, by providing the research community and regulatory and healthcare authorities with an information source on the practical steps needed for cell and gene therapy development. To achieve our aims, EuroGCT will adopt a highly structured system for coordinated management of information related to cell and gene therapy development and, from this, will implement an ambitious programme of online and direct stakeholder information provision and engagement. All outputs will be delivered in 7 European languages, to ensure broad accessibility, and will be rigorously evaluated against measurable objectives throughout the project duration. The proposed consortium comprises leading cell and gene therapy-related organisations and basic and clinical research labs across Europe, including new member states; together with experts in product development, ethical, legal and societal issues, and in evaluating clinical outcomes; patient representatives; and science communicators. It thus is uniquely placed to develop a world-leading cell and gene therapy information resource and to meet the challenge outlined in Topic SC1-HCO-19-2020.

In recent years, nucleic acids (NAs) have contributed significantly to advancing the diagnosis and treatment of diseases such as cancer, infectious and rare diseases. Breakthrough technologies like genome editing tool CRISPR/Cas9, direct RNA sequencing, multi-omics analysis procedure for NAs analysis, bioinformatics and machine learning for data analysis, and targeted delivery systems based on lipid nanoparticles (LNPs) prove the increasing interest in NAs applicability. However, the full potential of NAs is yet to be unlocked, and the translation of NAs into clinical practice is still facing many methodological and technological limitations such as low detection sensitivity, limited sequencing capacity, lack of analytical methods for NAs therapeutics, and inadequate in vivo delivery. INT2ACT brings together 6 academic research units and 5 industrial partners to address these limitations by establishing new methods for detecting and analysing NAs in patient liquid biopsies, boosting available procedures for direct RNA sequencing, developing new methods for the synthesis and analysis of antisense oligonucleotides (ASO) libraries, identifying new RNA targets, and optimise NA therapeutics delivery systems. The concept of harnessing NAs in the realm of medicine opens doors to an array of possibilities, including the development of therapeutic vaccines for cancer and innovative ASO-based therapies for addressing a multitude of genetic disorders. While advancing NAs’ research and technologies, INT2ACT will also contribute to forming the next generation of highly skilled experts through an interdisciplinary and intersectoral training programme delivered to 15 Doctoral Candidates. The network-wide training programme is designed to ensure that all INT2ACT fellows will have the skills for a successful career in or outside of research in any sector.

Disruptive technologies for bone regeneration must be able to tackle complex fracture environments which have developed into non-union bone defects. These types of fracture are common and increasingly prevalent when considering the rise in osteoporosis cases. Bioengineered bone graft systems need to be able to guide the regrowth of new bone into substantial voids and therefore implants pre-seeded with mineralising cells are of significant clinical interest. We will implement a surgical co-administration of two robust technologies 1) a granular graft material with a highly osteogenic coating that presents relevant biologics very efficiently and 2) pre-differentiated osteogenic adipose mesenchymal stromal cells (MSCs) that together will underpin efficient bone regeneration. Within the project we aim to take these two technologies into GMP and ISO rated manufacture as required for any clinical therapy. We will then implement these therapies in pre-clinical studies to obtain efficacy and safety data to support a full clinical trial application. The novel technologies will be developed into a new medical device and a new cellular therapy with pre-clinical validation for their co-administration. This modular application of two highly advanced therapies is itself highly novel in terms of clinical strategy and by the end of the project we aim to have made the required regulatory and technical developments to submit them for clinical trial. In parallel to the core therapy we will expand the therapeutic pipeline by replacing the granular graft with 3D printed polymeric scaffold, again including including a highly osteogeneic coating, as a carrier for the cell therapy. Targeting even larger bone defects, this scaffold will be co-administered with the cellular therapy in pre-clinical efficacy studies.