Gene delivery from the E3 region of replicating human adenovirus: evaluation of the E3B region
Gene delivery from the E3 region of replicating human adenovirus: evaluation of the E3B region
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DOI：
10.1038/sj.gt.3301509
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发表时间：
2001-08-01
期刊：
影响因子：
5.1
通讯作者：
Hermiston, T
中科院分区：
文献类型：
--
作者：
Hawkins, LK;Hermiston, T
成功的癌症疗法需要解决与人类肿瘤相关的复杂性。肿瘤和病毒生物学的研究已经取得进展，复制病毒现在被设计为人类癌症的潜在治疗方法。人类癌症的复杂性决定了成功的治疗需要联合疗法。为此，我们专注于开发复制腺病毒的基因传递能力，使用非必需的 E3 区转录单元作为治疗性转基因插入的靶位点。利用 E3 区域的内源表达机制（启动子、剪接、polyA），我们发现治疗性转基因 TNF 可从 E3B 区域有效表达，并具有独特的晚期基因表达动力学。讨论了潜在的临床应用。
Successful therapies for cancer need to deal with the complexity associated with the human tumor. Studies of tumor and viral biology have progressed to a point where replicating viruses are now being engineered as potential treatments for human cancers. The complex nature of human cancers dictates that successful treatments will require combination therapies. To this end, we have focused on developing the gene delivery capacity of the replicating adenovirus, using the non-essential E3 region transcription unit as a target site for therapeutic transgene Insertions. Utilizing the endogenous expression machinery of the E3 region (promoter, splicing, polyA) we show that a therapeutic transgene, TNF, is efficiently expressed from the E3B region and with exclusive late gene expression kinetics. Potential clinical applications are discussed.