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Self-Assembling Gene Delivery Systems

It is widely believed that non-viral gene delivery systems may increase safety and overcome tissue tropism limitations associated with viral based gene therapies. Cationic liposome based gene delivery currently accounts for 9 to 12 % of ongoing gene therapy clinical trials in the United States and Europe. Polycation based gene delivery is in an earlier development stage, however, studies in vitro and in vivo have demonstrated that they are very promising. Complexes of polycations with DNA result in major improvements in the control of size, charge, and hydrophilic-lipophilic characteristics of the transfecting species compared to other non-viral systems.

Low solubility is a general disadvantage of those systems. To overcome this problem, cationic block copolymers consisting of poly(ethylene oxide) and polycation segments were developed (Bioconjugate Chemistry 6:639-643, 1995). These copolymers form soluble block ionomer complexes with nucleic acids, resulting in neutralization of the DNA charges, DNA condensation and DNA stabilization. An increase in stability, transport, and activity of antisense oligonucleotides was demonstrated with cationic copolymers using cell models and in vivo. For example, in collaboration with Professor Sayon Roy (Boston University) reduction of fibronectin expression by intravitreal administration of antisense oligonucleotides with cationic copolymers has been demonstrated (Nature Biotechnology 17:476-479, 1999).