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

2015; Springer Nature; Volume: 22; Issue: 7 Linguagem: Inglês

10.1038/gt.2015.25

1476-5462

Danielle Weber‐Adrian, Emmanuel Thévenot, Mary O’Reilly, Wendy Oakden, Margarete K. Akens, Nicholas Ellens, Kelly Markham-Coultes, A Burgess, Joel Finkelstein, Albert Yee, Cari Whyne, Kevin D. Foust, Brian K. Kaspar, Greg J. Stanisz, Rajiv Chopra, Kullervo Hynynen, Isabelle Aubert,

Mechanical Circulatory Support Devices

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 × 108, 2 × 109 and 7 × 109 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 × 109 and 7 × 109 VG g−1 leads to robust GFP expression in FUS-targeted regions of the spinal cord. At a dose of 2 × 109 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.