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Gene delivery to the spinal cord using MRI-guided focused ultrasound.
Weber-Adrian, D; Thévenot, E; O'Reilly, M A; Oakden, W; Akens, M K; Ellens, N; Markham-Coultes, K; Burgess, A; Finkelstein, J; Yee, A J M; Whyne, C M; Foust, K D; Kaspar, B K; Stanisz, G J; Chopra, R; Hynynen, K; Aubert, I.
Affiliation
  • Weber-Adrian D; 1] Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Thévenot E; 1] Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • O'Reilly MA; Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
  • Oakden W; 1] Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Akens MK; 1] TECHNA Institute, University Health Network, Toronto, Ontario, Canada [2] Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
  • Ellens N; 1] Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Markham-Coultes K; Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
  • Burgess A; Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
  • Finkelstein J; 1] Department of Surgery, University of Toronto, Toronto, Ontario, Canada [2] Centre for Spinal Trauma, Division of Orthopaedic Surgery, Sunnybrook Research Institute, Toronto, Ontario, Canada.
  • Yee AJ; 1] Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada [2] Department of Surgery, University of Toronto, Toronto, Ontario, Canada [3] Centre for Spinal Trauma, Division of Orthopaedic Surgery, Sunnybrook Research Institute, Toronto, Ontario, Canada.
  • Whyne CM; 1] Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada [2] Department of Surgery, University of Toronto, Toronto, Ontario, Canada [3] Centre for Spinal Trauma, Division of Orthopaedic Surgery, Sunnybrook Research Institute, Toronto, Ontario, Canada.
  • Foust KD; Department of Neuroscience, Ohio State University and Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
  • Kaspar BK; Department of Neuroscience, Ohio State University and Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
  • Stanisz GJ; 1] Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Chopra R; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Hynynen K; 1] Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Aubert I; 1] Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Gene Ther ; 22(7): 568-77, 2015 Jul.
Article in En | MEDLINE | ID: mdl-25781651
ABSTRACT
Non-invasive gene delivery across the blood-spinal cord barrier (BSCB) remains a challenge for treatment of spinal cord injury and disease. Here, we demonstrate the use of magnetic resonance image-guided focused ultrasound (MRIgFUS) to mediate non-surgical gene delivery to the spinal cord using self-complementary adeno-associated virus serotype 9 (scAAV9). scAAV9 encoding green fluorescent protein (GFP) was injected intravenously in rats at three dosages 4 × 10(8), 2 × 10(9) and 7 × 10(9) vector genomes per gram (VG g(-1)). MRIgFUS allowed for transient, targeted permeabilization of the BSCB through the interaction of focused ultrasound (FUS) with systemically injected Definity lipid-shelled microbubbles. Viral delivery at 2 × 10(9) and 7 × 10(9) VG g(-1) leads to robust GFP expression in FUS-targeted regions of the spinal cord. At a dose of 2 × 10(9) VG g(-1), GFP expression was found in 36% of oligodendrocytes, and in 87% of neurons in FUS-treated areas. FUS applications to the spinal cord could address a long-term goal of gene therapy delivering vectors from the circulation to diseased areas in a non-invasive manner.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Spinal Cord / Spinal Cord Diseases / Genetic Therapy / Green Fluorescent Proteins Type of study: Diagnostic_studies Limits: Animals Language: En Journal: Gene Ther Journal subject: GENETICA MEDICA / TERAPEUTICA Year: 2015 Type: Article Affiliation country: Canada
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Spinal Cord / Spinal Cord Diseases / Genetic Therapy / Green Fluorescent Proteins Type of study: Diagnostic_studies Limits: Animals Language: En Journal: Gene Ther Journal subject: GENETICA MEDICA / TERAPEUTICA Year: 2015 Type: Article Affiliation country: Canada