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Intravenous Infusion of AAV for Widespread Gene Delivery to the Nervous System

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Adeno-Associated Virus Vectors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1950))

Abstract

The central nervous system (CNS) is a fascinating and intricate set of biological structures that we have yet to fully understand. Studying the in vivo function of the CNS and finding novel methods for treating neurological disorders have been particularly challenging. One difficulty is correcting genetic disorders afflicting the CNS in a targeted manner. Recombinant adeno-associated viruses (rAAVs) have emerged as promising therapeutic tools for treating genetic defects of the CNS, due to their excellent safety profile and ability to cross the blood-brain barrier (BBB). While stereotactic injection of AAV is promising for localized gene delivery, it is less desirable for some applications because of the technique’s invasiveness and limited intraparenchymal spread. Alternatively, intravascular administration can achieve widespread delivery of rAAV to the CNS. In this chapter, we will discuss the prevalent routes of administration to deliver rAAV to the CNS via intravenous (IV) injection in mice. We will highlight key considerations for using rAAV, and the advantages and disadvantages of each administration method. We will also briefly discuss intravenous delivery in larger animal models, factors that may impact experimental interpretations, and outlooks for clinical translation.

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Author information

Author notes

  1. Dominic J. Gessler and Phillip W. L. Tai contributed equally to this work.

Authors and Affiliations

  1. Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA

    Dominic J. Gessler, Phillip W. L. Tai, Jia Li & Guangping Gao

  2. Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, MA, USA

    Dominic J. Gessler, Phillip W. L. Tai, Jia Li & Guangping Gao

  3. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA

    Dominic J. Gessler, Phillip W. L. Tai, Jia Li & Guangping Gao

Authors
  1. Dominic J. Gessler
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  2. Phillip W. L. Tai
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  3. Jia Li
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  4. Guangping Gao
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Corresponding author

Correspondence to Guangping Gao .

Editor information

Editors and Affiliations

  1. Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA

    Michael J. Castle

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© 2019 Springer Science+Business Media, LLC, part of Springer Nature

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Gessler, D.J., Tai, P.W.L., Li, J., Gao, G. (2019). Intravenous Infusion of AAV for Widespread Gene Delivery to the Nervous System. In: Castle, M. (eds) Adeno-Associated Virus Vectors. Methods in Molecular Biology, vol 1950. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9139-6_8

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  • DOI: https://doi.org/10.1007/978-1-4939-9139-6_8

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9138-9

  • Online ISBN: 978-1-4939-9139-6

  • eBook Packages: Springer Protocols

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