Gene delivery to the spinal cord using MRI-guided focused ultrasound

D. Weber-Adrian, E. Thévenot, M. A. O'Reilly, W. Oakden, M. K. Akens, N. Ellens, K. Markham-Coultes, A. Burgess, J. Finkelstein, A. J.M. Yee, C. M. Whyne, K. D. Foust, B. K. Kaspar, G. J. Stanisz, R. Chopra, K. Hynynen, I. Aubert

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)568-577
Number of pages10
JournalGene Therapy
Volume22
Issue number7
DOIs
StatePublished - Jul 3 2015

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

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. (2015). Gene delivery to the spinal cord using MRI-guided focused ultrasound. Gene Therapy, 22(7), 568-577. https://doi.org/10.1038/gt.2015.25