CARTHAGO · Cartilaginous tissue regeneration by non-viral gene therapy; taking the hurdles towards efficient delivery

Cartilaginous tissue regeneration by non-viral gene therapy; taking the hurdles towards efficient delivery

Diseases of the musculoskeletal system impose a substantial burden on Western societies, which is ever increasing with ageing of the population. Amongst the diseases with most impact are osteoarthritis (OA) and chronic low back pain (CLBP) caused by intervertebral disc (IVD) degeneration, involving the cartilaginous tissues of these organs, being main causes of loss of disability-adjusted life years. Moreover, absenteeism poses a substantial economic burden on society. Despite the severity of the problems, medical solutions currently are limited and consist mainly of highly invasive surgery that replaces or immobilises the joint. Significant effort worldwide is aimed at helping the joint and IVD heal themselves by regenerative medicine, using stem cells or growth factors to regenerate the tissue, yet very few of these strategies have entered the clinic. Non-viral gene therapy has the potential to overcome these hurdles, due to its high specificity and, hence, safety, longevity of effects, and cost-effectiveness. However, the tight extracellular matrix of cartilaginous tissue does not contain blood vessels for transport and distribution of the therapeutic nucleic acids, posing a challenge to the delivery of gene activity modifying agents, in addition to prevention of extracellular and intracellular degradation of the therapeutic nucleic acids. Furthermore, in the public opinion gene therapy is conceived as a potentially hazardous strategy, and awareness and adequate information of the public is critical to enhance well-informed adoption. In CARTHAGO, together with 15 Early Stage Researchers (ESRs) we have addressed these challenges through an integrated research and training programme focused on 1) cell delivery and efficiency of gene modulation, 2) tissue and organ delivery tools; 3) repair in tissue and organ culture; 4) in vivo imaging of regeneration and gene therapy efficacy; and 5) responsible research and innovation. We have generated novel insights as well as new tools and concepts that will not only advance research in the field of gene therapy for cartilaginous tissue regeneration, but will also be of great interest to other scientific disciplines including nucleic acid therapy, biomaterials, gene delivery, regenerative medicine, orthopaedics in general, and research ethics. This will benefit the development of better treatment of musculoskeletal disorders as well as of other diseases eligible for nonviral gene therapy, contributing to the future accessibility of safe and effective therapy to patients and healthcare professionals. In addition, our project has delivered a next generation of young scientists trained to tackle the current challenges of gene therapy who can become our future scientific leaders in relevant fields.

Data: CORDIS, © European Union