Basic research on cerebellar gene therapy using lentiviral vectors

Cerebellum. 2012 Jun;11(2):443-5. doi: 10.1007/s12311-011-0330-x.

Abstract

Postmitotic neurons are resistant to gene delivery. However, lentiviral vectors allow the introduction of a foreign gene efficiently into neurons without significant toxicity to the infected cells (Sawada et al., Cerebellum 9(3):291-302, 2010). In addition, these vectors show a high tropism for neurons, and the transgenes they carry have been shown to be continuously expressed for at least a couple of years (Hirai, Cerebellum 7(3):273-8, 2008). We developed a method to express a foreign gene efficiently in cerebellar Purkinje cells in vivo (Takayama et al., Neurosci Lett 443(1):7-11, 2008; Torashima et al., Brain Res 1082(1):11-22, 2006, The Eur J Neurosci 24(2):371-80, 2006). Using our method, various experiments were carried out to study the pathophysiology of the cerebellum, including the investigation of a cerebellum-specific gene of unknown function, the generation and analysis of a mouse model of the spinocerebellar ataxia, and the rescue of an ataxic phenotype in mutant mice by introducing a defective gene or a therapeutic gene into the Purkinje cells. Here, we introduce our recent studies on expressing transgenes in the cerebellum using lentiviral vectors.

Publication types

  • Review

MeSH terms

  • Animals
  • Cerebellar Diseases / therapy*
  • Disease Models, Animal
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Lentivirus / genetics*
  • Mice
  • Mice, Knockout
  • Purkinje Cells / physiology
  • Spinocerebellar Ataxias / genetics
  • Spinocerebellar Ataxias / therapy