Nano‐Self‐Assembly of Nucleic Acids Capable of Transfection without a Gene Carrier

Nonviral gene carriers based on electrostatic interaction, encapsulation, or absorption require a large amount of polymer carrier to achieve reasonable transfection efficiencies. With cationic nanoparticles, for example, genes interact only with the surface of the nanoparticles, resulting in a low surface area to volume ratio (SA/V = 3/r). A large volume of carrier, therefore, is required to deliver a small copy number of genes. In this study, it is demonstrated that a nano‐self‐assembly of nucleic acids transfects itself into cells spontaneously, without the need for a gene carrier. The cellular uptake of this nanoassembly occurs through a number of endocytosis mechanisms. Once within the cell, the nanoassembly can escape endolysosomal vesicles and facilitate gene transfection. This nano‐self‐assembly consisting of zinc and plasmid DNA or siRNA, termed the Zn/DNA or Zn/siRNA nanocluster, is formed through the binding of Zn²⁺ ions to the phosphate groups of nucleic acids. The method described in this paper represents a new platform for carrier‐free gene delivery that can be used to deliver any plasmid DNA or siRNA without the requirement for a specific modification in the nucleic acids or complicated steps to prepare dense particles.