Mucin Glycoprotein Nanoparticles Enable a Selective Antisense Therapy for Oncogenic MicroRNAs

MicroRNAs (miRNAs) are critical regulators of gene expression, and their dysregulated expression has been implicated in the context of various diseases. Despite their therapeutic potential, the physicochemical instability and off‐target effects of miRNA‐targeting therapeutics pose significant challenges. To address this, the first antisense formulation is here developed based on highly biocompatible mucin glycoproteins, where the molecular cargo, synthetic DNA strands, has a dual functionality: stabilizing the structure of mucin glycoproteins into nanoparticles and enabling sequence‐specific binding to oncogenic miRNA. These condensed nanoparticles leverage the intrinsic properties of mucins and can be modified with targeting ligands to enhance the specificity of cellular uptake. Findings demonstrate that mucin nanoparticles demonstrate therapeutic potential by inhibiting tumor growth in vivo. This presented approach not only enhances the specificity of nucleic acid delivery but also opens the door for the development of personalized diagnostics and therapies for diseases characterized by cell‐specific overexpression of RNAs.