Cristina De Giorgi
Development of polymeric nanoparticles for gene delivery to Duchenne muscular distrophy.
Rel. Valentina Alice Cauda, Cristina Fornaguera, Marta Guerra Rebollo. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2026
Abstract
Duchenne Muscular Dystrophy (DMD) is a severe, X-linked recessive genetic disorder characterized by progressive muscle degeneration due to the total absence of the dystrophin protein. While traditional viral gene therapies aim to replace the missing gene, persistent tissue inflammation and impaired endogenous regeneration limit their clinical success. Pathological overexpression of miR-106b in satellite stem cells acts as a molecular brake, reinforcing deep quiescence and blocking myoblast proliferation. Consequently, a dual therapeutic approach that corrects the genetic mutation while simultaneously promoting muscle regeneration is highly needed. This thesis aims to develop and validate a targeted, non-viral polymeric platform based on oligo-modified poly(β-amino esters) (OM-PBAEs) to safely deliver genetic material to skeletal muscle cells.
To achieve tissue-specific targeting, the platform exploits the compensatory overexpression of α7β1 integrin on dystrophic tissue by functionalizing the nanoparticles (NPs) with the AAVMYO peptide
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