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We're excited to share our new publication in the International Journal of Polymeric Materials and Polymeric Biomolecules: "In vitro characterization of polymeric nanoparticles encapsulating plasmid DNA for gene therapy".

Abstract: Gene therapy is a promising clinical approach for treating or preventing genetic diseases by directly targeting disease-causing mutations. Despite the potential for gene therapy in addressing a broad range of genetic diseases, the development of these techniques remains in its early stages. A key challenge in the field is the development of approaches that efficiently deliver modified genetic material to intended biological targets, but minimize degradation and off-target effects. Biomedical polymeric nanoparticles (PNPs) can enhance gene therapy delivery by encapsulating, protecting, and releasing therapeutic compounds within target cells. However, their clinical translation is hindered by poor efficacy and storage instability. To address these challenges, we formulated Envoyer nanoparticles, a novel natural polymer-based delivery system. Here, we evaluate the stability and transfection efficiency of Envoyer nanoparticles in multiple human cell lines. In HEK293T cells, Envoyer nanoparticles (50–70 nm) encapsulating green fluorescent protein (GFP) plasmid DNA (pDNA) achieved a transfection efficiency of >80%, outperforming lipofectamine controls (~60%). InPANC1 pancreatic cancer cells, known for being difficult to transfect, Envoyer nanoparticles also demonstrated superior efficacy compared to lipofectamine controls. Notably, commonly used commercially available nanoparticles failed to produce GFP expression under similar conditions. Preliminary mechanistic studies suggest that Envoyer nanoparticle internalization occurs viaclathrin-independent endocytosis. Furthermore, we show that Envoyer nanoparticles maintain stability and transfection efficiency after storage for 2 months at 4 °C and −80 °C. Collectively, these findings highlight the potential of Envoyer nanoparticles as a stable and efficient gene delivery platform for future clinical applications in gene therapy.