GENE-ACTIVATED MATRICES (GAMS) - CONCEPT, LIMITATIONS AND FUTURE DEVELOPMENTS

Abstract

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Gene-activated matrices (GAMs) were described for the first time >15 years ago. These systems are combinations of biomaterials with gene therapeutics for application in regenerative medicine. Ideally, these implantable or injectable materials would offer efficient, preferably non-viral, gene delivery of active morphogens for effective regeneration whilst providing a biocompatible carrier matrix, which constitutes an environment supporting tissue regeneration. Despite initial promising results and high expectations for future therapeutic use, there are still no approved products in clinical use. This scenario potentially represents both an untapped opportunity for drug developers and a potential dead end in clinical translation. This presentation will therefore provide an overview of previously investigated approaches and types of GAMs, detail background information on the history of GAM development as well as describe potential mechanisms of drug delivery using GAMs. Furthermore, current concepts of advanced GAMs from our own work and those of other groups, and currently performed clinical studies will be presented. This information will be discussed in context with current developments in the field and risks associated with clinical translation. It will highlight potential issues within the preclinical development stage, regulatory hurdles and the reasons why adoption of these promising advanced therapeutic medicinal products (ATMPs) into clinical practise is not a straightforward process. Finally, this presentation will provide an outlook for future advanced versions of GAMs and their potential for the treatment of musculoskeletal disorders.