European Network for the Advancement of Clinical Gene Transfer and Therapy: EC funded network of excellence fostering interaction of all stakeholders in the field in order to facilitate and help harmonise Ethical, Quality, Safety, Efficacy and Regulatory issues. This NoE prolongs and extends the action of the former Euregenethy1 & 2 networks supported by EC-DG research FP4 & FP5 programmes.
The role of the European Network for the Advancement of Clinical Gene Transfer and Therapy (CLINIGENE) is to mobilise efficiently all interested parties, mostly involving academic research and production centers together with companies, patients' groups and regulatory bodies. Our main goal is to integrate multidisciplinary research in order to decipher the key elements which can lead to improved safety and clinical efficacy of gene transfer / therapy medicinal products, i.e. for clinical applications. Control and test methods may be applied as platforms for particular gene transfer products. Besides quality control, safety is of germane concern since in the event where the treatment would be proven safe, it could be administered early enough in the course of the disease to achieve genuine cure, so that clinical gene transfer may be called therapy.
The added value of CliniGene:
The CliniGene outreach
The CliniGene Network of Excellence, funded by the European Commission’s 6th Framework programme, has created both critical mass and momentum towards high quality gene transfer research at the level of basic science and its translation into well-designed clinical trials. Like all EU funded NoEs, it is time-limited, and will finish in its present format mid-2011. However, plans are underway to create a sustainable not-for profit structure that will preserve the expertise that CliniGene has created and master the momentum underpinning gene transfer research and its safe, effective clinical applications. This would result in the eventual formation of a non-profit “European Institute for Clinical Gene and Cell Therapy” to promote good practice and develop standards that will define good manufacturing practice (GMP) in gene transfer research. This Institute could implement and streamline European and international exchange of information and experience, the holding of workshops, seminars, conferences and other events, as well as the setting-up and editing, promotion and distribution of publications in any form, submission of expert advisory opinions, and cooperation with European and international public and non- government organisations. Such an Institute would be well positioned to respond quickly to the changing demands of a rapidly developing area of science. This would provide the opportunity not only to incorporate novel scientific and technical possibilities, but also to create the appropriate ethical, regulatory and public communication frameworks necessary to secure public endorsement and legitimisation for gene transfer research.
A special attention has been brought to the field of emerging technologies, translating into new collaborations funded through flexi-funds as a start-up mechanism intended for feasibility studies. In fact, the opportunities for joint applications between two (or more) labs and compete for flexifunds, has resulted in a huge number of high-quality original programmes. Over 66 collaborative projects have now been successfully funded following a stringent review process. The NoE will continue to encourage interaction in the main emerging fields which have been identified. Altogether, with this internal collaborative flexi- funds programme, an emerging vector platform has build up addressing the bottleneck problem of translational gene therapy research towards improved safety/efficacy.
In order to streamline the clinical translation of the most advanced technologies, the Joint Research Programme has developed and concentrates on four main directions:
- Safety and efficacy improved integrating vectors since predicting or even controlling the fate of transgenes integration is a major priority in the field [Gabriel et al, 2009; Montini et al, 2009; Mödlich et al, 2009; Hacein-Bay et al, 2008; Howe et al, 2008, Ott et al, 2006; Stein et al, 2010). Progress in this regard is likely to pave the way to the treatment of numerous conditions, noticeably accessible by ex-vivo gene-manipulation of stem cells, whether intended at repairing the cell defect like with hemoglobinopathies, Wiskott-Aldrich syndrome or Fanconi's anemia (Cohen-Haguenauer & al, 2006), or with view to enzyme replacement therapy like with adrenoleukodystrophy (Cartier N & al, 2009) or ADA-deficiency (Aiuti & al, 2009).
i. Organisation of a “hands-on” exchange programme in order to allow scientists who are directly involved in the iPS technical activity to visit collectively each others’ laboratories and benefit from each other’s expertise at the bench;
ii. Holding a main EU-based conference: e-CHIP
Finally, the paramount issue of vector production and manufacture has translated into a vision for the building of a Pan-European Vector infrastructure (PEVI) the description of which appears under GeneCellPro in the section dedicated to Facilities below. In fact, one key bottleneck of translating innovative technologies from bench-to-bedside is related to the production of the retargeted cell-type specific vectors or alternative serotypes (Cattaneo et al, 2008; Ciron et al, 2009; Duke et al, 2009). As high-titre vector preparation strongly depends on the capsid or envelope, the production efficiency substantially varies in between different vector types and according to the design of the transgene cassette (Funke et al, 2009). The ability to produce high-titer vectors that are capable of achieving increased gene transfer efficiency and expression in the desired target cells while preventing expression in non-target cells and genotoxicity, are measurable outcomes and addresses a current unmet need in the field of gene therapy. The primary focus of PEVI will be to fine-tune engineering in order to maintain the ability to produce improved vectors at high-titers. This is an essential requirement for translating vectors with improved safety features in confronting advanced technologies to the compulsory scale-up phase.
The NoE has adopted an integrated approach aiming at a high level education, training and human mobility of post-doctoral scientists, doctors and pharmacists in order to support a European dimension of highly specialised researchers, health professionals and managers with a view to fostering the clinical development process in collaboration with the ESGCT (European Society of Gene & Cell Therapy) with which a robust and mutually rewarding collaboration has been settled. In addition, contacts have been established with other EC-funded Gene Therapy –related research programme in order to streamline novelty and optimise dissemination.