Intranasal administration of the growth-compromised HSV-2 vector ΔRR prevents kainate-induced seizures and neuronal loss in rats and mice
Intranasal administration of the growth-compromised HSV-2 vector ΔRR prevents kainate-induced seizures and neuronal loss in rats and mice
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DOI：
10.1016/j.ymthe.2005.12.013
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发表时间：
2006-05-01
影响因子：
12.4
通讯作者：
Aurelian, Laure
中科院分区：
文献类型：
--
作者：
Laing, Jennifer M.;Gober, Michael D.;Aurelian, Laure
神经退行性疾病的基因治疗的靶点和递送平台的鉴定是临床挑战。我们描述了一种新的范例，其中的神经保护基因是单纯疱疹病毒2型（HSV-2）抗凋亡基因ICP 10 PK和载体是生长的承诺HSV-2突变体ARR。ARR通过鼻内给药。对大鼠和小鼠无毒。在不存在病毒复制和晚期病毒基因表达的情况下，ICP 10 PK在ARR处理的动物的海马体中表达至少42天。其表达受AP-1扩增环调控。在大鼠和小鼠中，鼻内递送ARR可预防红藻氨酸诱导的癫痫发作、神经元损失和炎症。这些数据表明，ARR是神经退行性疾病的一个有前途的治疗平台。
Identification of targets and delivery platforms for gene therapy of neurodegenerative disorders is a clinical challenge. We describe a novel paradigm in which the neuroprotective gene is the herpes simplex virus type 2 (HSV-2) antiapoptotic gene ICP10PK and the vector is the growth-com promised HSV-2 mutant ARR. ARR is delivered intranasally. It is not toxic in rats and mice. ICP10PK is expressed in the hippocampus of the ARR-treated animals for at least 42 days in the absence of virus replication and late virus gene expression. Its expression is regulated by an AP-1 amplification loop. Intranasally delivered ARR prevents kainic acid-induced seizures, neuronal loss, and inflammation, in both rats and mice. The data suggest that ARR is a promising therapeutic platform for neurodegenerative diseases.