Nuclear gene delivery: the Trojan horse approach

The nuclear envelope represents a formidable barrier to the transfer of plasmids to the cell nucleus, particularly in nondividing cells. The probability of intact plasmids arriving in the nucleus by a passive process is extremely low. There is substantial evidence in the literature that describes the transport of macromolecules, including plasmids, to the nucleus as a very inefficient process, and so far attempts to affect the active transport through the nuclear pores have achieved limited success. Several approaches have been attempted to improve nuclear transport of plasmids, including the condensation of plasmids to unimolecular complexes of minimal hydrodynamic diameter to favour passive transport through the nuclear pore complex, and the incorporation of nuclear localisation signals in the plasmid or in the delivery system to enhance the active transport of plasmids through the nuclear pores.