LONG-TERM GENE-EXPRESSION AND PHENOTYPIC CORRECTION USING ADENOASSOCIATED VIRUS VECTORS IN THE MAMMALIAN BRAIN
LONG-TERM GENE-EXPRESSION AND PHENOTYPIC CORRECTION USING ADENOASSOCIATED VIRUS VECTORS IN THE MAMMALIAN BRAIN
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DOI：
10.1038/ng1094-148
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发表时间：
1994-10-01
期刊：
影响因子：
30.8
通讯作者：
DURING, MJ
中科院分区：
文献类型：
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作者：
KAPLITT, MG;LEONE, P;DURING, MJ
腺相关病毒（AAV）载体是非致病性的整合DNA载体，其中所有病毒基因被去除并且辅助病毒被完全消除。为了在脑的有丝分裂后细胞中评估该系统，我们发现含有lacZ基因的AAV载体（AAVlac）导致体内注射后长达三个月的β-半乳糖苷酶的表达。将表达人酪氨酸羟化酶（AAVth）的第二载体注射到单侧6-羟基多巴胺损伤大鼠的去神经纹状体中。酪氨酸羟化酶（TH）免疫反应性可检测到纹状体神经元和胶质细胞长达四个月，我们还发现与AAVlac对照组相比，AAVth治疗的损伤大鼠的行为恢复显着。安全、稳定的TH基因转移到失神经支配的纹状体内可能为帕金森病的基因治疗提供了可能。
Adeno-associated viral (AAV) vectors are non-pathogenic, integrating DNA vectors in which all viral genes are removed and helper virus is completely eliminated. To evaluate this system in the post-mitotic cells of the brain, we found that an AAV vector containing the lacZ gene (AAVlac) resulted in expression of P-galactosidase up to three months post-injection in vivo. A second vector expressing human tyrosine hydroxylase (AAVth) was injected into the denervated striatum of unilateral 6-hydroxydopamine-lesioned rats. Tyrosine hydroxylase (TH) immunoreactivity was detectable in striatal neurons and glia for up to four months and we also found significant behavioural recovery in lesioned rats treated with AAVth versus AAVlac controls. Safe and stable TH gene transfer into the denervated striatum may have potential for the genetic therapy of Parkinson's disease.