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.