GenE-HumDi Action functions are divided in eight Working Groups (WG1-7). Members voluntarily join the WGs according to their specific disciplinary interactions and collaborations, and are led by WG elected leader. Although the GenE-HumDi colleagues are chosen on the basis of highest professional skill team, there is no disparity of gender or age.
This WG will be focused on Action management and will providing the right framework conditions of anonymization to promote exchange material between partners. Ensuring compliance with confidentially of the shared data and material between partners. And, this will provide appropriate information about
the Action and the achievement of the different WGs.
Main Tasks and activities
- Administration and coordination of networking and dissemination activities of partners.
- Scheduling the meetings amongst the relevant COST members.
- Assistance in Short-Term Scientific Mission (STSM) management in order to explore opportunities in each WG and avail of the possibility of each member to host an STSM or Summer/Training School at their institute.
- A COST Action website will be one of the first tasks to be addressed. This web page will have a protected domain and a public domain. The first one, with a password-protected domain, will be a repository containing all the updates, internal material and announcements. A public domain website will give information on the Action and its progress, and will also give individual information on each WG. More details about this website are given in Dissemination WG.
- Documentation and reporting of Action progress to COST.
- Financial supervision and regulatory compliance.
This WG will be focused on the consolidation of all information related to efficacy and specificity of the different GE tools in order to established research priorities in the field. The WG2 will lead to the establishment of strong collaborations between different GE technologies.
Main Tasks and activities
- To map the existing endonuclease-Independ platforms (EIP) and their potential output in different applications. This specific task will be opened to include researchers from third countries (especially USA) in order to ensure more up-to-date information of the state of the art of this technology.
- To map the existing endonuclease-depend platforms and their potential output in different applications.
- Create multidisciplinary networks to work on specific objectives Consolidate research platforms through grant applications to national, European and international financial bodies/funders.
This WG will focus on the evaluation of the ex vivo delivery systems and to identify an ideal delivery method for each cell type and GE technology. The second main focus of this WG will be the evaluation of in vivo delivery systems and to identify the best method for each animal model and route of administration.
Main Tasks and activities
- Generating a map of the current delivery methods used for GE of the different cell types that are used for clinical applications. To date non-viral systems, based on ribonucleoparticles (RNP) or plasmids, are the ex vivo systems of choice to deliver the GE complex into the target cells.
The RNP or plasmids could be transfected or electroporated into the cells according to the cell type. The efficacy and specificity of GE of the different GE tools delivered by different methods will be compared and best systems for each cell type identified. - Generating a map of the current delivery methods used for in vivo GE in different animal models and in clinical settings. Including comparison of efficacy and specificity data for different GE tools delivered by different methods in each tissue/organ of interest.
The main objective of the corresponding WG is Mapping of the methodology and of the current state of knowledge for toxicity of delivery, for genotoxicity (inadvertent off-target, on-target, recombination events), for cell population bias and for in vivo off-target tissue modification of different GE platforms and applications. The Harmonization and standardization of cell population bias and of assaying inadvertent on-target, off-target and recombination as a prerequisite of clinical translation.
Main Tasks and activities
- The establishment of a standardized pipeline for the unbiased identification and quantification of CRISPR off-target sites for therapeutic applications.
- Mapping the status quo for the assessment of recombination events.
- Mapping the status quo for the assessment of cell population bias (lineage bias, bias for p53 level).
- Mapping the status quo for the assessment of off-target delivery by in vivo application.
- Guidelines for the assessment of GE-related safety issues, covering localized on- and off-target events, recombination events, cell population lineage bias and in vivo off-target tissue delivery.
- The comparison of the different constrains in the HDR-mediated gene editing in the most primitive HSPCs, and how the HDR may be enhanced.
The principal aim of this WG is to map the status quo for GE translation in Europe for the treatment of inherited rare diseases, cancer, and infectious diseases. And also, to create a roadmap for manufacturing, adoption of protocols and integration in clinical procedures in order to find out potential investors that could fund the development of a clinical trial related to gene editing.
Main Tasks and activities
- Identification of translational GE hubs/centres of excellence.
- The creation of a committee of scientific advisors specialized in the topic that could assess the potential of a precise strategy to go into the clinic and provide advice to its development.
- The Establishment of a committee of scientific advisors specialized in the topic that could assess the potential of a precise strategy to go into the clinic and provide advice to its development.
- Identification of a clinical trial pipeline for GE-based therapies of rare diseases, cancers and infectious diseases. The evaluation of different GE strategies to target Hematopoietic stem cells in Fanconi anaemia cells in vitro, the sickle cell disease and beta-thalassemia, collagen VI deficiency and Emery Derfuss muscular dystrophy.
- Integration of GE/ATMP protocols into clinical routine.
- Assessment of centralized and decentralized manufacturing options and supply chains in Europe.
- Roadmap for clinical translation of GE-based therapies for rare diseases, cancers and infectious diseases.
- Fostering a suitable dose scaling technique for estimation of clinical first-in-man dosed from preclinical data for gene editing approaches.
- Develop practical workshops that cover the main steps to move into the clinic.
- Divulgate the translational research conducted by GenE-HumDi groups to help them find investors.
- Establish a GE expert team to establish research priorities required to advance GE into the clinic.
The principal aim of this WG is the evaluation of the actual situation of European facilities to provide a cost- effective sourcing for GMP-sources of gene editing based medicines to establish guidelines for the production of cost-effective GMP gene editing based medicines and to promote the Intellectual property management between the different partners.
Main Tasks and activities
- Evaluation of the market and technology, conduct a report of technological surveillance where the evolution of technology, projections, scenarios, time to market and competitive advantages are included. To perform a market research study and competitive analysis on gene editing based medicines including the following tasks: (i) Market opportunity. Target niche; (ii) Definition of targeted market, sales by category (product, territory, class and market share (sales peak, defining at least three different scenarios), positioning, market drivers and barriers.
- The purchase of market studies conducted by specialized independent analyst (GlobalData, MedTrack, Datamonitor) will be planned; (iii) Current and future potential competence identification, evolution, currently marketed competitive and developing products, competitive dynamics, potential collaborations, potential customers and suppliers; (iv) Identification of incentives for the development of such products, trends in the regulatory environment and other aspects that influence the potential market to be considered, (v) SWOT analysis.
- To analyse regulatory requirements for the commercialization of gene editing based medicines.
- This task will perform an analysis of the requisites and steps to take in order to obtain authorization for the commercialization of gene editing based medicines in the relevant healthcare authorities. Guidelines for the production of cost-effective and GMP compliant gene editing based medicines will be created.
- Intellectual property rights management. To establish a broad strategy for the identification of Intellectual property and the protection of its rights (IPR) for future gene editing based medicine products, as well as possible technology transfer models for future products (licenses, codevelopment, corporate spin-off) taking into account the regulation framework.
The main objective of the regulatory WG is to ensure the regulatory adequacy of non-clinical models and methods employed to assess the efficacy and safety of different in vivo and ex vivo GE tools. And to promote the elaboration of regulatory guidelines for the translation of GE tools to the clinic.
Main Tasks and activities
- An international workshop will be organized covering ATMPs regulation, with substantial experience and expertise in this field. It is planned to bring together international experts of the gene editing field to discuss the state-of-the-art in gene editing around the three regulatory pillars forming the basis for clinical use of ATMPs: 1) quality including manufacturing and control of the (investigational) medicinal product, 2) non-clinical testing in adequate animal models for efficacy and safety prior to clinical use and 3) clinical development including clinical protocol suitability (patient cohort, dosing, exclusion /inclusion criteria, etc.).
- A white paper summarizing the outcome of the workshop and, if possible, formulating regulatory recommendations for clinical implementation of gene editing will be written and published.
- Selecting the appropriate non-clinical regulatory studies for GE tools is challenging. One problem is the species-specificity of some GE tools and the potential immunogenicity of nucleases. Thus, homologous models and the use of different complementary non-clinical models (in silico, in vitro or in vivo) is required. Also, for safety studies, appropriate tools have to be validated to address tissue- specific off-target toxicity. For these purposes, we will work with WG3 and WG4 to establish the adequacy of non-clinical models and methods for regulatory approval of GE technologies.
- To promote and participate in the development of GE guidelines for clinical translation.
- The translation of GE technologies to the clinic presents many regulatory and ethical hurdles. We will work towards the development of clear international guidelines and will be in communication with European agencies and Scientific Societies to participate in the elaboration of the necessary GE guidelines for the translation of these products to the patients, considering specific GE tools and delivery systems.
The main objective of this WG is the dissemination of the results of the Action and the integration of research and analysis results in order to reduce the knowledge fragmentation between partners, and to promotes popular science using social media.
Main Tasks and activities
- An Action website will be set up, including details of all Action members, ongoing activity and key document.
- The elaboration of a communication and dissemination plan.
- The organization of several workshops and meeting with all WGs.
- The dissemination of the activities and results using mainstream social media (Twitter, Instagram, LinkedIn) to reach non-specialized audiences. Participate in national and international initiatives that aim to make science visible (The Day of the Woman in Science, The Day of the Rare Diseases, etc.).
- Priming the interaction among research groups and patient associations.
