Department of Human Physiology, Centre for Neuroscience, Flinders University, GPO Box 2100, Adelaide, South Australia 5001, Australia.
J Control Release. 2012 Jan 30;157(2):183-9. doi: 10.1016/j.jconrel.2011.08.026. Epub 2011 Aug 26.
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.
非病毒基因治疗系统被认为比病毒传递更安全。本文综述了最近的研究，描述了新型的非病毒基因向中枢神经系统的传递，特别强调了使用针对特定受体的抗体（称为免疫基因）进行受体介导的基因传递。通过使用可以在神经元内逆行运输的靶向剂，如抗体，非病毒基因治疗可以将基因递送到血脑屏障保护的特定神经元。描述了有效的非病毒基因治疗的组成部分，包括 DNA/RNA 载体、受体介导的内吞作用、内体逃逸和核进入。此外，还讨论了可以用于改善体内递送的隐形剂，如聚乙二醇。免疫基因作为肌萎缩侧索硬化症等致命疾病的治疗剂具有重要意义，但在真正有效的治疗方法得以实现之前，还需要进行更多的体内研究来确认其疗效。
