Cationic and non-condensing polymer-based gene delivery
INTRODUCTION The course of action of exogenous gene delivery to a mammalian cell proceeds through the following general pathway: formation of small DNA containing particles, uptake of the particles into the cell, entrance of the particles into the cytoplasm, transport of intact DNA to the nucleus and finally expression of delivered gene. The delivery process may be thwarted at any one of these many steps, resulting in reduced overall transfection efficiency. Viruses have evolved the machinery to proceed through each of these phases with ease, allowing their DNA to reach the nucleus and be expressed in high quantities. This unique property has led many researchers to reverse engineer these viruses to produce highly efficient gene transfer vectors without the associated harmful effects. However, these vectors are limited by an immune response, a limited capacity to carry DNA, and a short shelf-life. In an attempt to overcome these issues, an alternate approach to gene delivery was devised using entirely synthetic carriers. One such family of synthetic carriers utilizes polycationic polymers to condense DNA via electrostatic interactions, thus facilitating its cellular uptake. Another approach utilizes neutral amphiphilic polymers that bind to DNA via hydrogen bonding but do not condense it. Currently, the major drawback of these gene delivery systems is the much lower transfection efficiencies than those observed in viral systems. Thus, a majority of research in this area is devoted to increasing transfection efficiency while simultaneously gaining a better understanding of how both polycationic and non-condensing polymers help mediate gene delivery.