Peptide-DNA Co-Assembled Nanoparticles as a Nonviral Vector for Gene Delivery with High Transgene Expression

Nonviral vectors for gene therapy are a safer alternative to viral vectors that elicit a harmful immune response. Artificial viruses combine the strengths of viral and nonviral vectors and have emerged to be safe and efficient gene delivery vectors. Herein, we report the development of peptide–DNA coassembled nanoparticles as a new efficient vector for gene delivery with high transgene efficiency. The key to our success is to introduce several rationally designed functional short peptide modules: (1) a pH-sensitive segment, (2) an endosomal interruption segment, (3) a cell penetration peptide with high positive charges, (4) a nuclear localization signal peptide with positive charges, (5) aromatic groups to tune the hydrophobic/hydrophilic ratio, and (6) redox-sensitive residues. These peptide–DNA coassembled nanoparticles achieved efficient DNA delivery with transfection efficiency over 90% in a serum-containing medium. This work demonstrates the effectiveness of the module-based design approach and lays the groundwork for potential biomedical applications of peptide-based biomaterials.