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

作者：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^*

来源：Gene Therapy, 2015, 22(7): 568-577.

DOI：10.1038/gt.2015.25

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.

• 出版日期2015-7