Vector development for spatiotemporal controlled gene expression.

WP leader: TUM (Members)

Partners involved: ARI (Members), NUI Galway (Members), OZB (Members), BIM (Members), EMC (Members), INSERM (Members)

Gene vectors are a central element of the GAMBA project as they are used for the controlled expression of transgenes on command and demand in order to drive cell differentiation and anti-inflammatory processes in a purposeful manner.

The aim of the work package is providing multifunctional vectors as part of a multifunctional construction kit from which elements are chosen according to the specific needs of spatiotemporal control under various settings.

Confidential communication between members of this workpackage:  Workpackage Discussion Room (Member Area)

Development of a biomimetic hyaluronan-based polymer as carrier of gene vectors.

WP leader: ARI (Members)

Partners involved: TUM (Members),  NUI Galway (Members), OZB (Members), BIM (Members), INRC (Members), INSERM (Members)

The aim of this WP is to develop, characterise and optimise temperature-sensitive biomimetic hyaluronan compositions to be used as injectable embedding matrices in combination with calcium phosphate ceramic and superparamagnetic nanoparticles.

These will be tested amongst others for their ability to allow spatiotemporal controlled release of gene vectors and/or encoded factors, and their biocompatibility (e.g. encapsulation of human mesenchymal stem cells hMSC). Materials will be prepared and selected for use in vitro and in animal studies.

Confidential communication between members of this workpackage:  Workpackage Discussion Room (Member Area)

Biomimetic Calcium Phosphate Bioceramics granules as carriers for gene vectors.

WP leader: BIM (Members)

Partners involved: TUM (Members), ARI (Members), NUI Galway (Members), OZB (Members), EMC (Members), INRC (Members), INSERM (Members)

This work package deals with a different kind of biomaterials based on proprietary MBCP. The aim is to adapt and optimise MBCP as carriers for gene vectors and demonstrate in model systems in vitro gene delivery and inducible gene expression.

Confidential communication between members of this workpackage:  Workpackage Discussion Room (Member Area)

Attenuation of inflammation for osteochondral defect repair by immune modulation.

WP leader:  NUI Galway (Members)

Partners involved: TUM (Members), ARI (Members), EMC (Members), INRC (Members)

This work package deals with the immune modulation of in OA with the aim of facilitation of repair of pathologies in the injured joint. Optimized conditions for spatiotemporal gene expression and controlled inducible cytokine release will be established in this work package.

Confidential communication between members of this workpackage:  Workpackage Discussion Room (Member Area)

Spatiotemporal control of growth factor gene delivery for cartilage repair.

WP leader: EMC (Members)

Partners involved: TUM (Members), ARI (Members), BIM (Members), INRC (Members), INSERM (Members)

Define the conditions needed for cartilage formation by MSCs to determine the specific construct requirements and to test a subset of these constructs/vectors for chondrogenic induction capacity.

Confidential communication between members of this workpackage:  Workpackage Discussion Room (Member Area)

Spatiotemporal growth factor delivery for bone formation.

WP leader: INRC (Members)

Partners involved: TUM (Members), ARI (Members), BIM (Members), EMC (Members), INSERM (Members)

The aim of this work package is to define the conditions needed for endochondral bone formation, to inform on the specific construct requirements and to test a subset of these constructs/vectors for bone induction capacity in vivo.

Confidential communication between members of this workpackage:  Workpackage Discussion Room (Member Area)

Large animal models for OA.

WP leader: ARI (Members)

Partners invovlved: TUM (Members), NUI Galway (Members), BIM (Members), EMC (Members), INRC (Members), INSERM (Members)

In this WP, depending on the out come of WP3 (inflammation), WP4 (cartilage) and WP5 (bone) a large animal models (goat) is proposed to assess osteochondral repair. Ideally, if the WPs 3-5 will be successful in identifying the best conditions to repair cartilage and bone and to release the anti-inflammatory molecule, the animal model we will propose will be an osteochondral defect in the femoral condyle of the goat. Alternatively, specific models addressing cartilage or bone repair separately or modulating inflammation will be proposed.

Confidential communication between members of this workpackage:  Workpackage Discussion Room (Member Area)

Linking GAMBA to society through science-society dialogues on chances, risks and ethical aspects.

WP leader: SCID (Members)

Partners involved: TUM (Members), ARI (Members), NUI Galway (Members)

A key element of this project is the involvement of members of society into the research on innovative treatments of arthritis. We will set up a two-way dialogue at eye level between patients / citizens and leading European scientists in three European countries. In the so-called patient and citizen panels participants are first introduced to the field of innovative research on arthritis through expert presentations during the panels and a hearing with experts selected by the citizens in the citizen panel. In a second step, participants negotiate about this input and then compile patient-/ citizen-reports supported by independent facilitators. Therefore, the main objective of this work package is to discuss the chances, risks and ethical aspects of innovative arthritis treatments with lay people and to develop communication strategies to provide clinics, interested companies as well as the media and a broader public with balanced, professionally developed and scientifically sound information. Two main questions will be answered by the dialogue measures: 1. What do lay people (patients / citizens) want to know about GAMBA? What are their associations with GAMBA? What specific topics are they interested in from their special point of view as concerned patients / interested citizens? 2. What are lay people’s recommendations to the scientific world, to regulators, industry and media regarding the chances, risks, ethical/social aspects of GAMBA?

With a gender workshop we will raise awareness for the participation of women in science, especially in leading positions, as at graduate student level there are often more women than men, but in leading positions there is a male majority.

Confidential communication between members of this workpackage:  Workpackage Discussion Room (Member Area)

Public communication between members and patients / citizens: Patient and Citizen Panels Discussion Room

Disseminating and exploiting GAMBA.

WP leader: TUM (Members)

Partners involved: ARI (Members), NUI Galway (Members), OZB (Members), BIM (Members), EMC (Members), INSERM (Members), SCID (Members)

This work package is designed to disseminate information on the research performed to the consortium, the scientific community, the industry and lay public throughout Europe and to ensure proper exploitation of GAMBA results.

Confidential communication between members of this workpackage:  Workpackage Discussion Room (Member Area)

Management Activities.

WP leader: TUM (Members)

The management activities ensure that all formal, incl. budgetary and reporting actions are performed correctly, timely and according to the rules and regulations established by the European Commission and the consortium agreement. This also includes that knowledge and innovation are properly managed and exploitation of results is promoted and that measures for patent applications are prepared.

Confidential communication between members of this workpackage:  Workpackage Discussion Room (Member Area)