Pseudotype-dependent lentiviral transduction of astrocytes or neurons in the rat substantia nigra.
Pseudotype-dependent lentiviral transduction of astrocytes or neurons in the rat substantia nigra.
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DOI：
10.1016/j.expneurol.2010.10.016
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发表时间：
2011-03
影响因子：
5.3
通讯作者：
Greenamyre, J. Timothy
中科院分区：
文献类型：
--
作者：
Cannon, Jason R.;Sew, Thomas;Montero, Laura;Burton, Edward A.;Greenamyre, J. Timothy
关键词：
基因转移到中枢神经系统提供了强有力的方法，在体内的基因功能和基因-环境相互作用的研究，除了载体的治疗转基因的基因治疗。本研究的目的是确定假型慢病毒载体在大鼠黑质中表现出的嗜性模式，以评估其在帕金森病实验模型中的基因转移效用。编码GFP报告基因的同基因慢病毒载体颗粒用来源于水泡性口炎病毒（VSV）、Mokola病毒（MV）、淋巴细胞性脉络丛脑膜炎病毒（LCMV）或莫洛尼鼠白血病病毒（MuLV）的包膜糖蛋白假型化。成年雄性刘易斯大鼠接受单侧立体定向输注载体到黑质;三周后，通过GFP的免疫组织学检测确定病毒转导模式。不同的假型引起转基因表达的限制和不同的细胞群体。VSV和MV假型转导中脑神经元，包括黑质多巴胺能神经元的子集。相反，LCMV和MuLV假型慢病毒仅在星形胶质细胞中产生转基因表达;先前显示介导LCMV或MuLV进入的受体的细胞分布不能解释星形胶质细胞的有限转导。这些数据表明，假型慢病毒载体将有助于向大鼠黑质进行实验性基因转移。特别是，神经元和星形胶质细胞靶向载体的可用性将允许关键基因产物的细胞自主和细胞非自主功能在体内解离。
Gene transfer to the central nervous system provides powerful methodology for the study of gene function and gene-environment interactions in vivo, in addition to a vehicle for the delivery of therapeutic transgenes for gene therapy. The aim of the present study was to determine patterns of tropism exhibited by pseudotyped lentiviral vectors in the rat substantia nigra, in order to evaluate their utility for gene transfer in experimental models of Parkinson’s disease. Isogenic lentiviral vector particles encoding a GFP reporter were pseudotyped with envelope glycoproteins derived from vesicular stomatitis virus (VSV), Mokola virus (MV), lymphocytic choriomeningitis virus (LCMV), or Moloney murine leukemia virus (MuLV). Adult male Lewis rats received unilateral stereotactic infusions of vector into the substantia nigra; three weeks later, patterns of viral transduction were determined by immunohistological detection of GFP. Different pseudotypes gave rise to transgene expression in restricted and distinct cellular populations. VSV and MV pseudotypes transduced midbrain neurons, including a subset of nigral dopaminergic neurons. In contrast, LCMV and MuLV-pseudotyped lentivirus produced transgene expression exclusively in astrocytes; the restricted transduction of astroglial cells was not explained by the cellular distribution of receptors previously shown to mediate entry of LCMV or MuLV. These data suggest that pseudotyped lentiviral vectors will be useful for experimental gene transfer to the rat substantia nigra. In particular, the availability of neuronal and astrocytic-targeting vectors will allow dissociation of cell-autonomous and cell non-autonomous functions of key gene products in vivo.
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影响因子：
56.9
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通讯作者：
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