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Lentiviral Vector-Mediated Gene Transfer and RNA Silencing Technology in Neuronal Dysfunctions

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Book cover Lentivirus Gene Engineering Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 614))

Abstract

Lentiviral-mediated gene transfer in vivo or in cultured mammalian neurons can be used to address a wide variety of biological questions, to design animal models for specific neurodegenerative pathologies, or to test potential therapeutic approaches in a variety of brain disorders. Lentiviruses can infect nondividing cells, thereby allowing stable gene transfer in postmitotic cells such as mature neurons. An important contribution has been the use of inducible vectors: the same animal can thus be used repeatedly in the doxycycline-on or -off state, providing a powerful mean for assessing the function of a gene candidate in a disorder within a specific neuronal circuit. Furthermore, lentivirus vectors provide a unique tool to integrate siRNA expression constructs with the aim to locally knockdown expression of a specific gene, enabling to assess the function of a gene in a very specific neuronal pathway. Lentiviral vector-mediated delivery of short hairpin RNA results in persistent knockdown of gene expression in the brain. Therefore, the use of lentiviruses for stable expression of siRNA in brain is a powerful aid to probe gene functions in vivo and for gene therapy of diseases of the central nervous system. In this chapter, I review the applications of lentivirus-mediated gene transfer in the investigation of specific gene candidates involved in major brain disorders and neurodegenerative processes. Major applications have been in polyglutamine disorders, such as synucleinopathies and Parkinson’s disease, or in investigating gene function in Huntington’s disease, dystonia, or muscular dystrophy. Recently, lentivirus gene transfer has been an invaluable tool for evaluation of gene function in behavioral disorders such as drug addiction and attention-deficit hyperactivity disorder or in learning and cognition.

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    Jean-Luc Dreyer

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Correspondence to Jean-Luc Dreyer .

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  1. Div. Patogenesi dei Retrovirus, Centro Nazionale AIDS, Viale Regina Elena 299, Roma, 00161, Italy

    Maurizio Federico

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Dreyer, JL. (2010). Lentiviral Vector-Mediated Gene Transfer and RNA Silencing Technology in Neuronal Dysfunctions. In: Federico, M. (eds) Lentivirus Gene Engineering Protocols. Methods in Molecular Biology, vol 614. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-533-0_1

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  • DOI: https://doi.org/10.1007/978-1-60761-533-0_1

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-532-3

  • Online ISBN: 978-1-60761-533-0

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