Non-viral gene therapy systems are considered safer than viral delivery. This article reviews recent research describing novel, non-viral gene delivery to the central nervous system, with a special emphasis on receptor mediated gene delivery using antibodies (termed immunogenes) to specific receptors. By using targeting agents such as antibodies that can be retrogradely transported within neurons, non-viral gene therapies can deliver genes to specific neurons protected by the blood brain barrier. Components of effective non-viral gene therapy are described including DNA/RNA carriers, receptor-mediated endocytosis, endosomal escape and nuclear entry. In addition, stealth agents such as polyethylene glycol that can be used to improve in-vivo delivery are discussed. The value of immunogenes as therapeutic agents for fatal diseases such as Amyotrophic Lateral Sclerosis is significant but further in-vivo work to confirm efficacy is required before truly effective therapies can be achieved.