Intrathecal shRNA-AAV9 inhibits target protein expression in the spinal cord and dorsal root ganglia of adult mice

Human Gene Therapy Methods
Takashi HiraiTakanori Yokota

Abstract

Gene therapy for neurological diseases requires efficient gene delivery to target tissues in the central and peripheral nervous systems. Although adeno-associated virus is one of the most promising vectors for clinical use against neurological diseases, it is difficult to get it across the blood-brain barrier. A clinically practical approach to using a vector based on adeno-associated virus to decrease the expression of a specific gene in both the central and the peripheral nervous system has yet to be established. Here, we analyzed whether upper lumbar intrathecal administration of a therapeutic vector incorporating adeno-associated virus and short-hairpin RNA against superoxide dismutase-1 bypassed the blood-brain barrier to target the spinal cord and dorsal root ganglia. The therapeutic vector effectively suppressed mRNA and protein expression of endogenous superoxide dismutase-1 in the lumbar spinal cord and dorsal root ganglia. Moreover, neither neurological side effects nor toxicity due to the incorporated short-hairpin RNA occurred after the injection. We propose that this approach could be developed into novel therapies for motor neuron diseases and chronic pain conditions, such as complex regional pain syndrome, throug...Continue Reading

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Citations

Dec 11, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Takashi HiraiTakanori Yokota
Feb 18, 2016·Neural Plasticity·Seung-In ChoiSun Wook Hwang
Jan 16, 2015·Metabolic Brain Disease·Dominic SchombergDaniel Resnick
Oct 7, 2014·Frontiers in Molecular Neuroscience·Giridhar MurlidharanAravind Asokan
Nov 18, 2017·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Chen-Xi ZhengYa-Yun Wang
Jul 13, 2019·Neurological Research·Shuangli ZhangQinggang Meng

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Methods Mentioned

BETA
PCR
transfection

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