Discussion

Gene therapy presents an exciting opportunity to many diseases, but one of the technical hurdles is gene delivery. A wide range of cationic polymers has been used to condense DNA and aid their transfection into cells. However, the relative lack of control over the molecular architecture of these polymers means it is difficult to relate the structure of the complexes to their performance in promoting gene internalization within cells. In this work, a biocompatible polymer was used as a well-defined model vector for antisense oligonucleotide (ODN). Electrophoresis has been used to reveal the charge density of the polymer/ODN complexes. Small Angle Neutron Scattering (SANS) was used to determine the polymer/ODN complex size and structure. Transfection studies using HeLa cells indicated increased transfection efficiency with decreasing complex size and increasing cationic charge. This study demonstrates a strong link between the structure and charge of the gene complexes and their efficiency in gene transfection.