CliniGene - NoE

The 7 CliniGene technology platforms

Scientific platforms: Approach & methodology

The CliniGene-NoE has elected to accompany the development of novel protocols using cutting edge technology, rather than investigate in retrospect protocols already closed. Improved, higher- generation-technologies (Figure below) are expected to better translate into practical exemplification of rigorous new knowledge and hopefully clinical success which are currently showing into the picture. The network first started analysing the current bottlenecks. From the initial assessment of limitations, a better understanding has arised and potential solutions have been successfully addressed.

As mentioned, a strong integration plan has been inforced and a stepwise implementation adopted. All partners in the six technology platforms initiated work according to accurrate plans matching and adapting to the specific requirements of each technology under consideration. At months six, a workshop gathered all platforms on the occasion of the CliniGene satellite held at ESGCT meeting in Athens. The task-forces already formed commented on experience gathered & defined lines for improvement; from there, the three remaining platforms integrated: Non-viral vectors, Adenovectors and lentivectors. A special satellite on lentivectors was held in Athens as well. All six platforms exchange and feed-in the general biosafety task force (TF). After the first year of work in common , it was decided to establish a separate integrative TF, the immunotoxicology TF entering into force in order to better address in vivo immune barriers to gene transfer.

The integration of the seven CliniGene technology platforms within a core-structure including emerging technologies, biosafety & immunotoxicology task-forces is represented as follows:

This cartoon reflects on the high level of exchanges, indicative of a high added value from one technology to the next. In fact, during the two first annual meetings, task-forces presented work and exchanged in parallel sessions. This organisation was discontinued following partners' request to learn from the others. Indeed, this has increased networking during the past years as materialised by the general list of partners involved: " CliniGene NoE technology platforms".

Safety is being considered from both the pharmaco-toxicology, immunotoxicology and the virus safety sides (with specific coordination WPs addressing each: WP 1.4, WP1.5 and WP 1.6). Whatever the technology, viral safety assessement includes a series of common checkpoints to consider which need to be standardised. An important safety issue relates to vector integration with a concurrent risk of insertional mutagenesis. The Network is addressing potential improvement using a variety of experimental approaches, as mentioned in the joint programme and emerging technologies section (WP 3.3). In order to establish quality, common standards of reference have to be shared. The latter must be tested, broad consensus be reached and then agreed upon by both academic centers and companies specialising in the manufacture of gene transfer vectors for the purpose of human gene therapy. During the course of our programme, the need and specification of such standards have been identified from one vector system to the next since with distinct technologies, the requirements are diverse. Because of CliniGene successful networking, the need for a specific programme has emerged with matching funding in order to work out these consensus standards and methods, as planned as part of the GeneCellPro infrastructure project (or PEVI).

The NoE is currently working out platform databases for particular vectors with respect to their safety, efficacy and quality standards in order to accelerate the transit phase from research to clinical trials including emerging technologies (Activity 5).