Abstract

Nonviral gene carriers taking advantage of electrostatic interaction, encapsulation, or absorption to deliver genes require significantly larger amount of natural or synthetic carriers to achieve reasonable transfection efficiencies. With cationic nanoparticles, for example, genes interact only with the surface of nanoparticles, resulting in a low surface area to volume ratio (SA/ V = 3/ r ). Consequently this inefficiency demands a large volume of carrier to deliver a small amount of genes. In this study, we have demonstrated that a nano-self-assembly of nucleic acids transfects itself into cells spontaneously without the need of a gene carrier. The cellular uptake of this nanoassembly occurs through a number of endocytosis mechanisms. Once transported within the cell, the self-assembled nucleic acid nanoparticles can escape the endolysosomal vesicles and promote 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 project represents a new platform for carrier-free gene delivery that can be used to deliver any plasmid DNA or siRNA without the requirement for specific nucleic acid modifications or complicated steps to generate dense particles