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基于猴疱疹病毒的基因传递载体在体内的附加型维持

In vivo episomal maintenance of a herpesvirus saimiri-based gene delivery vector.

作者信息

Smith P G, Coletta P L, Markham A F, Whitehouse A

机构信息

Molecular Medicine Unit, University of Leeds, St James's University Hospital, UK.

出版信息

Gene Ther. 2001 Dec;8(23):1762-9. doi: 10.1038/sj.gt.3301595.

Abstract

Herpesvirus saimiri (HVS) has several properties that make it amenable to development as a gene delivery vector. HVS offers the potential to incorporate large amounts of heterologous DNA and infect a broad range of human cell lines. Upon infection the viral genome can persist by virtue of episomal maintenance and stably maintains heterologous gene expression. Here we report an evaluation of the in vivo properties of HVS, with a view to its development as a gene delivery system. We demonstrate for the first time, the long-term persistence of the HVS genome in tumour xenografts generated from HVS-infected human carcinoma cell lines. The HVS-based vector remained latent in the xenograft without spreading to other organs. Moreover, the long-term in vivo maintenance of the HVS genome, as a nonintegrated circular episome, provided efficient sustained expression of a heterologous transgene. These in vivo results suggest that HVS-based vectors have potential for gene therapy applications.

摘要

赛米利疱疹病毒(HVS)具有多种特性,使其适合开发成基因传递载体。HVS能够容纳大量异源DNA,并能感染多种人类细胞系。感染后,病毒基因组可通过游离型维持而持续存在,并稳定维持异源基因表达。在此,我们报告对HVS体内特性的评估,以期将其开发成一种基因传递系统。我们首次证明,HVS基因组在由HVS感染的人类癌细胞系产生的肿瘤异种移植物中能够长期持续存在。基于HVS的载体在异种移植物中保持潜伏状态,不会扩散到其他器官。此外,作为非整合环状附加体的HVS基因组在体内长期维持,可有效持续表达异源转基因。这些体内实验结果表明,基于HVS的载体在基因治疗应用方面具有潜力。

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