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Currently, research on polymers to be used as gene delivery systems is one of the most important directions in both polymer science and biomedicine. In this report, we describe a five-step procedure to synthesize a novel polymer–peptide hybrid system for gene transfection. The block copolymer based on the biocompatible polymer poly(2-methyl-2-oxazoline) (PMOXA) was combined with the biocleavable peptide block poly(aspartic acid) (PASP) and finally modified with diethylenetriamine (DET). PMOXA-b-PASP(DET) was produced in high yield and characterized by 1H NMR and FT-IR. Our biopolymer complexed plasmid DNA (pDNA) efficiently, and highly uniform nanoparticles with a slightly negative zeta potential were produced. The polymer–peptide hybrid system was able to efficiently transfect HEK293 and HeLa cells with GFP pDNA in vitro. Unlike the commonly used polymer, 25 kDa branched poly(ethylenimine), our biopolymer had no adverse effects on cell growth and viability. In summary, the present work provides valuable information for the design of new polymer–peptide hybrid-based gene delivery systems with biocompatible and biodegradable properties.
