• Publication: Adriana M. Ledo, Ana Senra, Héctor Rilo-Álvarez, Erea Borrajo, Anxo Vidal, María J. Alonso, Marcos García-Fuentes, RNA-activated matrices encoding transcription factors as primers of cell differentiation in tissue engineering, Biomaterials, Vol. 247, July 2020 https://doi.org/10.1016/j.biomaterials.2020.120016

Gene-activated matrices (GAMs) encoding pivotal transcription factors (TFs) represent a powerful tool to direct stem cell specification for tissue engineering applications. However, current TF-based GAMs activated with pDNA, are challenged by their low transfection efficiency and delayed transgene expression. Here, we report a GAM technology activated with mRNAs encoding TFs SOX9 (cartilage) and MYOD (muscle). We find that these mRNA-GAMs induce a higher and faster TF expression compared to pDNA-GAMs, especially in the case of RNase resistant mRNA sequences. This potent TF expression was translated into a high synthesis of cartilage- and muscle-specific markers, and ultimately, into successful tissue specification in vitro. Additionally, we show that the expression of tissue-specific markers can be further modulated by altering the properties of the mRNA-GAM environment. These results highlight the value of this GAM technology for priming cell lineage specification, a key centerpiece for future tissue engineering devices.

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