title: Intravenous delivery of adeno-associated viral vector serotype 9 mediates effective gene expression in ischemic stroke lesion and brain angiogenic foci.
abstract: OBJECTIVE
  Adeno-associated viral vector (AAV) is a powerful tool for delivering genes to treat brain diseases. Intravenous delivery of a self-complementary but not single-stranded AAV9 (ssAAV9) mediates robust gene expression in the adult brain. We tested if ssAAV9 effectively mediates gene expression in the ischemic stroke lesion and angiogenic foci.
  
  
  METHODS
  Focal ischemic stroke was induced by permanent occlusion of the left middle cerebral artery (MCAO) and focal angiogenesis was induced by injecting an AAV expressing vascular endothelial growth factor (AAV-VEGF) into the basal ganglia. ssAAV vectors that have cytomegalovirus (CMV) promoter driving (AAV-CMVLacZ) or hypoxia response elements controlling (AAV-H9LacZ) LacZ expression were packaged in AAV9 or AAV1 capsid and injected into mice through the jugular vein 1 hour after MCAO or 4 weeks after the induction of angiogenesis. LacZ gene expression was analyzed in the brain and other organs 5 days after LacZ vector injection.
  
  
  RESULTS
  LacZ expression was detected in the peri-infarct region of AAV9-CMVLacZ and AAV9-H9LacZ-injected MCAO mice and the brain angiogenic foci of AAV9-CMVLacZ-injected mice. Minimum LacZ expression was detected in the brain of AAV1-CMVLacZ-injected mice. Robust LacZ expression was found in the liver and heart of AAV-CMVLacZ-injected mice, but not in AAV9-H9LacZ-injected mice.
  
  
  CONCLUSIONS
  ssAAV9 could be a useful tool to deliver therapeutic genes to the ischemic stroke lesion or brain angiogenic foci.
authors.affiliation: University of California, San Francisco, Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, San Francisco, CA 94110, USA.
authors.forename: Fanxia
authors.initials: F
authors.lastname: Shen
authors.forename: Robert
authors.initials: R
authors.lastname: Kuo
authors.forename: Marine
authors.initials: M
authors.lastname: Milon-Camus
authors.forename: Zhenying
authors.initials: Z
authors.lastname: Han
authors.forename: Lidan
authors.initials: L
authors.lastname: Jiang
authors.forename: William L
authors.initials: WL
authors.lastname: Young
authors.forename: Hua
authors.initials: H
authors.lastname: Su
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000229:Dependovirus / Q000145:classification / Q000235:genetics; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000145:classification / Q000235:genetics; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D012703:Serotyping; D020521:Stroke / Q000235:genetics / Q000473:pathology / Q000628:therapy*