Efficientin vivogene transfection by stable DNA/PEI complexes coated by hyaluronic acid

Tomoko Itoa, Naoko Iida-Tanakab & Yoshiyuki Koyamaaa Department of Textile Science, Otsuma Women's University Graduate School, Sanbancho, Chiyoda-ku, Tokyo, 102-8357, Japanb Department of Food Science, Otsuma Women's University Graduate School, Sanbancho, Chiyoda-ku, Tokyo, 102-8357, JapanDepartment of Textile Science, Otsuma Women's University Graduate School, Sanbancho, Chiyoda-ku, Tokyo, 102-8357, Japan, 81 3 5275 6017, 81 3 5275 6932 koyama@otsuma.ac.jpPlasmid DNA was mixed with polyethyleneimine (PEI) and hyaluronic acid (HA) to afford ternary complexes with negative surface charge regardless of the mixing order. They showed reduced non-specific interactions with blood components. When DNA and PEI were mixed at a high concentration such as that used in in vivo experiments, they soon aggregated, and large particles were formed. On the other hand, pre-addition of HA to DNA prior to PEI effectively diminished the aggregation, and 10% (in volume) of the complexes remained as small particles with a diameter below 80 nm. Those negatively charged small ternary complexes induced a much stronger extra-gene expression in tumor than binary DNA/PEI complex after intratumoral or intravenous injection into the mice bearing B16 cells.