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rAd-shGirdin is an experimental gene therapy construct consisting of a recombinant adenoviral (rAd) vector that delivers short hairpin RNA (shRNA) designed to silence the expression of Girdin (also known as CCDC88A or Girders of actin filament). Girdin is a non-receptor guanine nucleotide exchange factor that plays a critical role in actin cytoskeleton remodeling, cell migration, and cancer progression. In pancreatic ductal adenocarcinoma, Girdin overexpression is associated with poor prognosis and resistance to chemotherapy. The mechanism of rAd-shGirdin involves the specific knockdown of Girdin mRNA, which in turn modulates autophagy pathways—specifically by disrupting the interaction between Girdin and the autophagy-related protein p62/SQSTM1. This disruption has been shown in preclinical models to increase the chemosensitivity of pancreatic cancer cells to gemcitabine, suggesting that Girdin acts as a negative regulator of chemotherapy response. This therapeutic approach is being investigated as a potential strategy to overcome chemoresistance in pancreatic cancer.
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