UPGRADE (Unlocking Precision Gene Therapy) is 5 years (2019-2024) collaborative project funded by the H2020 programme of the European Union.
The overall goal of UPGRADE is to overcome current limitations that are hindering broad application of gene therapy, improving the safety, efficiency and in vivo delivery of advanced medicinal products (AMPs) based on gene and epigenome editing.
UPGRADE involves eight partners from seven Countries, including a non-EU partner (from USA). Moreover, a panel of independent scientists from the Scientific Advisory Board will provide strategic guidance and support the partnership to ensure that the project’s results meet the objectives.
UPGRADE main objectives are to: i) improve efficiency and safety of novel and emerging genome and epigenome editing technologies; ii) precisely assess and enhance specificity of genome editing; iii) tailor delivery of the novel genome editing technologies for in vivo application; iv) characterize and circumvent the immunogenicity of the AMPs; v) translate these novel AMPs into novel treatment paradigms applicable to to prototypic diseases, some of which affect ; vi) successfully manage, disseminate and exploit the results obtained by the consortium.
Overall, UPGRADE will exploit and further develop disruptive new technologies for precision gene and epigenome editing and stringently characterize their specificity and cellular responses. It will then combine these improved technologies with advanced gene delivery approaches to generate prototypes of advanced medicinal products (AMP). The safety and efficacy profile of each AMP will be stringently validated in disease models paradigmatic for unmet medical need and potential long-term cure, if the limitations of current gene therapy strategies are overcome. These will AMPs represent versatile products portable to the treatment of several other diseases because of related pathogenesis or correction strategies, thus providing the basis for tackling diseases affecting large patient groups.
As such, UPGRADE will foster the competitiveness of EU pharmaceutical companies, deepening the understanding of the basic biological mechanisms underlying DNA damage response and repair, epigenetic regulation and immune sensing of exogenous components and making tangible improvements with a durable impact on the development of novel therapeutics across Europe.
UPGRADE objectives will be achieved through the activities carried out within ten operational workpackages, besides the management and ethics ones: Novel strategies to increase precision and efficacy of gene and epigenetic editing (WP1), Retargeting gene/vector integration (WP2), Genome-wide off-target profiling of gene-editing reagents (WP3), Viral and non-viral mediated delivery of genes and genome engineering components (WP4), Increase immune evasion of genome engineering components (WP5), Advanced genetic engineering of hematopoiesis (WP6), Novel strategies to target skeletal and cardiac muscle wasting in aging and disease conditions (WP7), Retinal degeneration (WP8), Expanding the breadth of liver directed gene therapy to include larger patient populations (WP9), Communication, stakeholders engagement, dissemination and exploitation (WP11).
Full project title: Unlocking Precision Gene Therapy
Grant Agreement number: 825825
H2020 Call: Better Health and care, economic growth and sustainable health systems
Topic: Innovation platforms for advanced therapies of the future
Duration: 1st January 2019 to 31st December 2023
Number of partners: 8
Project Coordinator: Luigi Naldini