Non-viral gene therapy for neurological diseases, with an emphasis on targeted gene delivery

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 invivo 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. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.