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.