Recombinant Sendai virus-mediated gene transfer into adult rat retinal tissue: Efficient gene transfer by brief exposure
Recombinant Sendai virus-mediated gene transfer into adult rat retinal tissue: Efficient gene transfer by brief exposure
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DOI：
10.1006/exer.2002.1177
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发表时间：
2002-07-01
影响因子：
3.4
通讯作者：
Sueishi, K
中科院分区：
文献类型：
--
作者：
Ikeda, Y;Yonemitsu, Y;Sueishi, K
为了确定重组仙台病毒（SeV）用于眼部基因转移的有效性，作者通过视网膜下注射将SeV介导的基因转移到成年大鼠的视网膜组织中。编码lacZ基因的重组SeV在视网膜色素上皮（RPE）中实现频繁的转基因表达（平均= 38.76%）。虽然基因转移到其他视网膜细胞是罕见的，这些发现是类似于以前的报告使用腺病毒。SeV在培养的RPE细胞中的峰值报告基因表达与相同滴度的腺病毒相似;然而，SeV在短暂的载体-细胞接触时间后达到高水平的表达，而腺病毒需要超过3小时进行有效的基因转移。在视网膜下腔中短暂SeV填充后，也在体内观察到该发现，因此可能在避免由于长期脱离导致的视网膜损伤方面提供临床优势。所观察到的SeV介导的基因在大鼠视网膜中的表达是短暂的。荧光素酶活性下降的初始阶段可以通过每日滴眼地塞米松来预防，这表明皮质类固醇敏感的宿主反应可能影响病毒的早期清除。免疫抑制剂环孢菌素A以剂量依赖性方式抑制转基因表达的晚期下降（2周），这表明细胞毒性T淋巴细胞应答在该阶段可能是重要的。这项工作代表了SeV介导的基因转移到眼组织的第一份报告，并确定重组SeV作为视网膜基因转移和基因治疗研究的新工具。(C)2002年爱思唯尔科学有限公司
To determine the usefulness of recombinant Sendai virus (SeV) for ocular gene transfer, the authors characterized SeV-mediated gene transfer to the retinal tissue of adult rats via subretinal injection. Recombinant SeV encoding the lacZ gene achieved frequent transgene expression in the retinal pigment epithelium (RPE) (mean = 38.76 %). while gene transfer to other retinal cells was rare, These findings are similar to those of previous reports using adenoviruses. Peak reporter gene expression of SeV in cultured RPE cells was similar to that of adenovirus at the same titer; however, SeV achieved high levels of expression after a brief vector-cell contact time, while adenovirus required over 3 hr for efficient gene transfer. This Finding was also observed in vivo following a brief SeV filling in the subretinal space, and may, therefore provide a clinical advantage in avoiding retinal damage due to prolonged detachment. The observed SeV-mediated gene expression in the rat retina was transient. The initial phase of the decrease in luciferase activity could be prevented by daily eye drops of dexamethasone, suggesting that the corticosteroid-sensitive host reaction may affect early clearance of the virus, The late decline of transgene expression (2 weeks) was inhibited by the immunosuppressant, cyclosporin A, in a dose-dependent manner, suggesting that the cytotoxic T-lymphocyte response may be important in this phase. This work represents the first report of SeV-mediated gene transfer to ocular tissue, and identifies recombinant SeV as a new tool for studies of retinal gene transfer and gene therapy. (C) 2002 Elsevier Science Ltd.