This tailored formulation demonstrated exceptional stability, significant cellular uptake, and intracellular release of saRNA assisted by endogenous RNase H. Consequently, it led to significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, resulting in notable inhibition of PDAC cell proliferation in vitro and effective suppression of tumor growth in a mouse model of PDAC. The gene discussed is CEBPA; the disease is neoplasm.