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

Author:
Weber-Adrian, D.  Thevenot, 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.  


Journal:
GENE THERAPY


Issue Date:
2015


Abstract(summary):

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 nonsurgical 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 x 10(8), 2 x 10(9) and 7 x 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 x 10(9) and 7 x 10(9) VG g(-1) leads to robust GFP expression in FUS-targeted regions of the spinal cord. At a dose of 2 x 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.


Page:
568---577


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