Targeted Gene Therapy for Ischemic Stroke

  • Fanxia Shen
  • Hua SuEmail author
Part of the Neuromethods book series (NM, volume 98)


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.

Key words

Adeno-associated viral vector serotype 9 Hypoxia response Gene transfer Ischemia Intravenous delivery Permanent distal middle cerebral artery occlusion Target gene expression in ischemic brain 


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Anesthesia and Perioperative Care, Center for Cerebrovascular ResearchUniversity of California, San FranciscoSan FranciscoUSA

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