Helper-dependent adenoviral vector-mediated gene transfer in aged rat brain.
Helper-dependent adenoviral vector-mediated gene transfer in aged rat brain.
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老年大鼠脑中辅助依赖性腺病毒载体介导的基因转移。
DOI：
10.1089/104303401750061249
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Yang,K
中科院分区：
文献类型：
--
作者：
Zou,L;Yuan,X;Zhou,H;Lu,H;Yang,K
将神经营养因子基因转移到大脑中可以减轻与年龄相关的缺陷，如神经元萎缩和记忆丧失，但缺乏合适的载体。毒性和免疫原性 第一代E1缺失腺病毒载体（fgAdv）的出现阻碍了基因转移在大多数中枢神经系统疾病中的应用。在这里，我们报告毒性较小和持久的基因 辅助依赖性腺病毒（hdAdv）介导的在老年大鼠脑中的表达。在海马内或脑室内接种载体后，通过X-Gal染色监测转基因表达， 与fgAdv介导的表达相比。通过免疫组织化学检测小胶质细胞、星形胶质细胞和浸润性巨噬细胞来评价宿主对这些载体的炎症和免疫应答， 以及细胞因子TNF-α和IL-1β的酶联免疫吸附试验。hdAdv介导的转基因表达持续超过183天，无论接种部位如何， 脑室内和海马内接种后，fgAdv-mediated表达分别为33天和66天。接种hdAdv也与激活的小胶质细胞数量减少有关。 细胞、星形胶质细胞和脑组织中的浸润性巨噬细胞。在hdAdv接种后，促炎细胞因子TNF-α和IL-1β的分泌最小，但在fgAdv接种后则没有。这些发现 提示hdAdv可为老年脑内治疗性基因转移提供一种安全有效的方法。
Transfer of the neurotrophin gene into brain can attenuate age-related deficits such as neuronal atrophy and memory loss, but a suitable vector for this procedure has been lacking. The toxicity and immunogenicity of first-generation adenoviral vectors with E1 deletion (fgAdv) prohibit the application of gene transfer in the majority of central nervous system disorders. Here, we report less toxic and persistent gene expression mediated by helper-dependent adenovirus (hdAdv) in aged rat brain. After intrahippocampal or intraventricular inoculation of the vector, transgene expression was monitored by X-Gal staining and compared with fgAdv-mediated expression. Host inflammatory and immune responses against these vectors were evaluated by immunohistochemical detection of microglia, astrocytes, and infiltrating macrophages, as well as by enzyme-linked immunosorbent assay of cytokines TNF-α and IL-1β. Transgene expression mediated by hdAdv persisted for more than 183 days regardless of inoculation site, as compared with 33 and 66 days for fgAdv-mediated expression after intraventricular and intrahippocampal inoculation, respectively. Inoculation with hdAdv was also associated with reduced numbers of activated microglial cells, astrocytes, and infiltrating macrophages in brain tissue. Secretion of the proinflammatory cytokines TNF-α and IL-1β was minimal after hdAdv but not after fgAdv inoculation. These findings indicate that hdAdv would provide a safe and effective means to transfer therapeutic genes into aged brain.
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中枢神经系统中辅助依赖性腺病毒载体（hdAd）介导的转基因表达延长。
DOI：
10.1006/mthe.2000.0104
发表时间：
2000
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy.
影响因子：
--
作者：
Zou,L;Zhou,H;Pastore,L;Yang,K
通讯作者：
Yang,K
大脑中腺病毒载体免疫反应的变化：小鼠品系、环境条件和启动的影响
影响因子：
5.1
作者：
Y. Ohmoto;M. Wood;H. Charlton;K. Kajiwara;V. Perry;K. Wood
通讯作者：
K. Wood
物种和菌株对白矿物油和石蜡的不同反应。
DOI：
--
发表时间：
1996
期刊：
Regulatory toxicology and pharmacology : RTP
影响因子：
--
作者：
Morgan Miller;E. Lonardo;R. D. Greer;C. Bevan;Doug Edwards;J. H. Smith;Jason Freeman
通讯作者：
Jason Freeman
影响大脑腺病毒载体基因治疗的免疫参数。
影响因子：
3.2
作者：
M. Parr;P. Wen;M. Schaub;S. Khoury;M. Sayegh;H. Fine
通讯作者：
H. Fine
NGF 体细胞基因转移至衰老大脑：行为和形态改善
影响因子：
5.3
作者：
Ks Chen;F. Gage
通讯作者：
F. Gage