Gene based therapeutic systems is a promising therapeutic area for the treatment of various diseases. Gene delivery systems are required to effectively deliver nucleotides into target cells. Nano-self-assembly systems based on binding affinity between Zinc and nucleotides was spontaneously formed nano-cluster through the binding of zinc ions to the phosphate groups of nucleic acids. This system could enhance delivery of DNA or siRNA into the cells without any polymers and cytotoxicity. Zinc/Nucleotides nano cluster was applied commercial polymer including polyethylenimine (PEI 25k), PEI 1.8k and poly-L-Lysine (PLL) to enhance delivery of nucleotide. It could enhance efficiency of gene delivery and reduced amount of polymer. It was also combined with targeting peptide without any modification. Zinc/nucleotide nano-self-assembly system may one of useful methods to deliver nucleotides for the treatment of disease and development of genetic engineered cells.