Unidad de Tumores Sólidos Infantiles

The CRISPR/Cas9 gene editing system has resulted in an extraordinary revolution in the field of gene therapy, opening up enormous possibilities for the treatment of human diseases. Although the system is extraordinarily effective in vitro and ex vivo, its use in vivo is limited by the difficulties involved in transferring the gene editing machinery specifically to the target cells. In this project we propose to use therapeutic extracellular vesicles (TEVs) to deliver the Cas9/sgRNA editing machinery and demonstrate its efficacy in the treatment of the epidermolysis bullosa (recessive dystrophic form), a genetic disease that severely affects the skin (known as butterfly skin disease). The specific objectives of the project under which the TFM will be developed are: 1) To design, produce and characterize specific TEVs for the treatment of epidermolysis bullosa; 2) To evaluate the efficiency and sensitivity of TEVs both in vitro and in vivo; 3) Functionalize TEVs to improve cell specificity and 4) Optimize large-scale TEV production. The results obtained will be used to determine the suitability of this strategy for preclinical studies in future projects and its possible clinical implementation in a later phase.