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Nanotechnologically reprogrammed cellular medicines

16th national competition for scientific and technical research

Gene and regenerative therapy

Senior Researcher : Marcos García Fuentes

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Research Centre or Institution : Centro Singular en Medicina Molecular y Enfermedades Crónicas. Universidad de Santiago de Compostela


The use of stem cells as therapeutic tools is associated with the regeneration of complex tissues and organs. However, these applications are currently restricted in clinical terms due to the lack of availability of stem cells, together with the difficulty of inducing conversion to target lines safely and efficiently. This proposal involves a cellular medicine platform based on priming lines with the potential characteristics of efficacy, safety and logistic convenience, turning them into tools for clinical use. The technology presented is based on the concept of directly reprogramming target cell lines, without going through a previous state of pluripotency ("line priming"). To achieve these aims, line priming will take place using a population of cells that are accessible and available in sufficient amounts, using synthetic nanovectors with a high level of biosafety. Finally, the primed cells will be integrated within biomimetic scaffolding able to direct the association of cells for the formation of structural tissues. This project is intended to achieve an initial proof of concept by priming functional human chondrocytes and neurons and then studying the possibility of assembling these cells for the formation of hyaline cartilage and layers of interconnected neurons.

During these first months of the project, work is being undertaken to optimise gene transfer methodology for line priming. More specifically, work is taking place on optimising the gene sequences using several synthetic and biosynthetic methods to promote the maximum expression of the transgenes introduced. Using these methods, up to 70% of adult stem cells express the transgene. This work will be complemented by another nanotechnological approach: the design of high transfectability synthetic nanovectors. Additionally, during these first months, a genetic sequence is being designed that is able to prime chondrogenic lines based on adult stem cells.

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