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Gene Delivery and Therapy for Neurological Disorders pp 191–202Cite as

Targeted Gene Therapy for Ischemic Stroke

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Part of the book series: Neuromethods ((NM,volume 98))

Abstract

Exogenous delivery of angiogenic and neuroprotective genes has been shown to enhance innate compensatory responses after ischemic injury. However, there are certain barriers in translating gene-based therapy to the clinical setting. For example, systemic delivery of genes into the brain is prevented by the blood–brain barrier (BBB); intraventricular delivery results in nonspecific distribution and gene expression; and stereotactic injection of vectors into the ischemic penumbra requires an invasive procedure that can cause additional damage. This chapter describes an adeno-associated viral (AAV) vector with two primary attributes that have the potential to overcome these problems. First, the vector contains hypoxia response elements (HREs) that restrict therapeutic gene expression to ischemic tissue. Second, AAV serotype 9 (AAV9) effectively penetrates the BBB, enabling intravenous administration. This chapter also illustrates the methods of constructing AAV vectors with hypoxia-inducible gene expression, generating the mouse permanent distal middle cerebral artery occlusion (pMCAO) model, standard assays to analyze brain injury and gene transfer, and effective behavior tests for the pMCAO model.

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Authors and Affiliations

  1. Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, 1001 Potrero Avenue, Box 1363, San Francisco, CA, 94110, USA

    Fanxia Shen & Hua Su M.D.

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  1. Fanxia Shen
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  2. Hua Su M.D.
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Correspondence to Hua Su M.D. .

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Editors and Affiliations

  1. Queen Mary University of London, London, United Kingdom

    Xuenong Bo

  2. Netherlands Institute for Neuroscience, Amsterdam, The Netherlands

    Joost Verhaagen

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Shen, F., Su, H. (2015). Targeted Gene Therapy for Ischemic Stroke. In: Bo, X., Verhaagen, J. (eds) Gene Delivery and Therapy for Neurological Disorders. Neuromethods, vol 98. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2306-9_8

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  • DOI: https://doi.org/10.1007/978-1-4939-2306-9_8

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