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 language | English (US) |
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Pages (from-to) | 568-577 |
Number of pages | 10 |
Journal | Gene Therapy |
Volume | 22 |
Issue number | 7 |
DOIs | |
State | Published - Jul 3 2015 |
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics