Tetrary gene delivery system for gene therapy and methods of its use

A method of forming a delivery system, comprising:

• binding a DNA or RNA molecule with polyethylenimine such that an end of the DNA or RNA molecule is exposed, wherein the polyethyienimine has a positive electrostatic charge, and wherein the end of the DNA or RNA molecule has a negative electrostatic charge;
• thereafter, capping the end of the DNA or RNA molecule that is exposed with a crosslinked polyspermine, the crosslinked polyspermine having an N/P ratio greater than 5 and wherein the crosslinked polyspermine has been crosslinked via reaction of a polyspermine and a disulfide crosslinker, the crosslinked polyspermine having a positive electrostatic charge such that the crosslinked polyspermine is electrostatically bonded to the end of the DNA or RNA molecule and a core is formed that includes the polyethylenimine, the DNA or RNA molecule, and the crosslinked polyspermine;
• and
• encapsulating the core with hyaluronic acid or alginate to form the delivery system, wherein the hyaluronic acid or alginate has a negative electrostatic charge, and wherein the hyaluronic acid or alginate is electrostatically bonded to the core, wherein the hvaluronic acid or alginate is present in a weight ratio of up to 50 comparing the weight of the DNA or RNA molecule.