Gene therapy involves the use of nucleic acids, either DNA or RNA for the treatment, cure, or prevention of human diseases. Synthetic cationic polymers are promising as a tool for gene delivery because of their high level of design flexibility for biomaterial construction and are capable of binding and condensing DNA through electrostatic interactions.
Our lab has developed a novel polymer (poly (polyethylene glycol-dodecanoate) (PEGD), a polyester of polyethylene glycol (PEG) and dodecanedioic acid (DDA). PEGD is a linear viscous polymer that self-assembles into a vesicle upon immersion in an aqueous solution. A copolymer of dodecanedioc acid and polyethylene glycol (PEG) was synthesized at a 1:1 ratio. Furmaric (FA) or itaconic acid (IA) was used to suppress DDA in the PEGD copolymer at an 80:20 ratio (DDA: furmaric/itaconic acid) to form the PEGDF/I variant. PEGDF/I are then modified through the Michael addition of Protamine Sulfate (PEGDF/I-PS) and Cys-Arg8 (PEGDF/I-CA) peptide to the carbon-carbon double bond on the polymer backbone to introduce a positive charge.
The modified PEGDF/I polymers were capable of binding and condensing DNA. Transfection of HEK 293 cells with pTurboGFP plasmid using modified PEGDF/I polymers was successful but showed varied efficiency. The PEGDF/I-CA polymer had around 30% transfection efficiency and was shown to be non-cytotoxic.
