ABSTRACT
Non-viral vector development has expanded into a broad area of research incorporating
diverse fields and technologies to essentially mimic what the virus does well: deliver
nucleic acids into cells. Viruses have evolved into highly efficient gene transfer agents
that exploit the cellular machinery to deliver the viral genome to the nucleus and ensure
viral propagation. As such, they have become useful recombinant agents for delivery of
therapeutic genes. One might wonder, then, why it is desirable to attempt an alternative
non-viral approach to gene delivery given the evolutionary advantage of the virus. One
major reason is simply that non-viral vectors are not viruses: they are not pathogenic
agents prone to mutation or recombination that could potentially produce emergent
species. Additionally, non-viral vectors are often less cytotoxic and immunogenic than
viruses. Moreover, for practical reasons, it is more facile to produce and test non-viral
vectors in pharmacologic amounts than attempt to manipulate the viral genome without
disrupting the ability to propagate the virus. A major drawback to non-viral vectors
in vivo, however, is the typically low yield of gene transfer compared to viruses. In some
cases, the stability of non-viral vectors in vivo is also questionable. Thus, to appreciate the
exploration of non-viral delivery to such specialized tissue as neuronal cells, it is
worthwhile examining the molecular and cellular requirements that one must consider for
non-viral vector development.