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Different Serotypes of Adeno-Associated Virus Vector- and Lentivirus-Mediated Tropism in Choroid Plexus by Intracerebroventricular Delivery.
Human Gene Therapy ( IF 3.9 ) Pub Date : 2020-03-04 , DOI: 10.1089/hum.2019.300
Xi Chen 1, 2, 3 , Yong He 2, 3 , Yu Tian 2, 3, 4 , Yue Wang 2, 3, 5 , Zhonghao Wu 2, 3, 5 , Tianlan Lan 2, 3, 5 , Haiyang Wang 2, 3 , Ke Cheng 2, 4, 6 , Peng Xie 1, 2, 3, 4
Affiliation  

Regulation of gene expression by viral vectors is an effective method for researchers to explore the function of gene products in a target tissue. The choroid plexus (CP) is an important target for gene therapy of neuropsychiatric diseases such as Alzheimer's disease and major depressive disorder. However, viral tropism in CP has not been well studied as a result of limited viral vector applications. To identify CP-specific viral vectors, we intracerebroventricularly administered six different serotypes of adeno-associated virus (AAV) vectors (AAV2/1, AAV2/5, AAV2/8, AAV2/9, AAV2-BR1, and AAV2-PHP.eB) and lentivirus in adult mice. Tropism in CP was compared among these viruses. We found that AAV2/5 and AAV2/8 displayed remarkable infections in CP, while AAV2/1 infected both ependymal cells and cells in the CP. Except for the low infection intensity of AAV2/9 and lentivirus in the CP, no infection intensity was found for CP tissues injected with AAV2-BR1 or AAV2-PHP.eB. Green fluorescence protein expression in the CP after AAV2/5 infection was confirmed by Western blotting. AAV2/5-mediated tropism in epithelial cells of the CP was verified by immunostaining with transthyretin. In this study, we identified for the first time that serotype-specific AAVs 5 and 8 may be robust research tools for intracerebroventricular gene delivery.

中文翻译:

通过脑室内递送在脉络丛中腺相关病毒载体和慢病毒介导的趋向性的不同血清型。

病毒载体调控基因表达是研究人员探索靶组织基因产物功能的有效方法。脉络丛(CP)是阿尔茨海默病和重度抑郁症等神经精神疾病基因治疗的重要靶点。然而,由于病毒载体应用有限,CP 中的病毒趋向性尚未得到很好的研究。为了识别 CP 特异性病毒载体,我们在脑室内注射了六种不同血清型的腺相关病毒 (AAV) 载体(AAV2/1、AAV2/5、AAV2/8、AAV2/9、AAV2-BR1 和 AAV2-PHP.eB ) 和成年小鼠中的慢病毒。在这些病毒之间比较了 CP 的趋向性。我们发现 AAV2/5 和 AAV2/8 在 CP 中表现出显着的感染,而 AAV2/1 感染了 CP 中的室管膜细胞和细胞。除了 CP 中 AAV2/9 和慢病毒的感染强度较低外,注射 AAV2-BR1 或 AAV2-PHP.eB 的 CP 组织未发现感染强度。通过蛋白质印迹证实 AAV2/5 感染后 CP 中的绿色荧光蛋白表达。AAV2/5 介导的 CP 上皮细胞的趋向性通过用转甲状腺素蛋白免疫染色来验证。在这项研究中,我们首次确定血清型特异性 AAV 5 和 8 可能是脑室内基因传递的有力研究工具。AAV2/5 介导的 CP 上皮细胞的趋向性通过用转甲状腺素蛋白免疫染色来验证。在这项研究中,我们首次确定血清型特异性 AAV 5 和 8 可能是脑室内基因传递的有力研究工具。AAV2/5 介导的 CP 上皮细胞的趋向性通过用转甲状腺素蛋白免疫染色来验证。在这项研究中,我们首次确定血清型特异性 AAV 5 和 8 可能是脑室内基因传递的有力研究工具。
更新日期:2020-02-14
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