A novel human artificial chromosome gene expression system using herpes simplex virus type 1 vectors
A novel human artificial chromosome gene expression system using herpes simplex virus type 1 vectors
复制标题
使用单纯疱疹病毒1型载体的新型人类人工染色体基因表达系统
作者：
D. Moralli;Kirsty M Simpson;R. Wade;Z. L. Monaco
人类人工染色体(HAC)载体是进行基因表达和互补研究的重要基因转移系统。我们描述了使用传染性单纯疱疹病毒1型(HSV-1)扩增载体进行传递的HAC技术的重大进展。这种高效的方法允许在胶质瘤、肾和肺来源的细胞中建立表达基因的HAC。我们还开发了HSV-1次黄嘌呤磷酸核糖基转移酶(HPRT)HAC载体，该载体能够产生功能性的HPRT表达HAC，弥补了人类细胞中的遗传缺陷。HSV-1 HAc扩增片段的转导效率比脂质体介导的转导效率高出几个数量级。对不同细胞类型的HAC稳定性的研究表明，重要的差异对HAC的发展和人类细胞中的基因表达具有重要意义。这是通过使用高效、高容量的病毒载体并确定与特定细胞类型的HAC不稳定相关的因素，在人类细胞中建立基因表达HAC的第一份报告。这项工作是对HAC技术和人类细胞HAC基因表达系统开发的重大进展。
Human artificial chromosome (HAC) vectors are an important gene transfer system for expression and complementation studies. We describe a significant advance in HAC technology using infectious herpes simplex virus type 1 (HSV‐1) amplicon vectors for delivery. This highly efficient method has allowed gene‐expressing HACs to be established in glioma‐, kidney‐ and lung‐derived cells. We also developed an HSV‐1 hypoxanthine phosphoribosyltransferase (HPRT) HAC vector, which generated functional HPRT‐expressing HACs that complemented the genetic deficiency in human cells. The transduction efficiency of the HSV‐1 HAC amplicons is several orders of magnitude higher than lipofection‐mediated delivery. Studies on HAC stability between cell types showed important differences that have implications for HAC development and gene expression in human cells. This is the first report of establishing gene‐expressing HACs in human cells by using an efficient, high‐capacity viral vector and by identifying factors that are involved in cell‐type‐specific HAC instability. The work is a significant advance for HAC technology and the development of HAC gene expression systems in human cells.
使用细菌人工染色体中 ICP27 删除的超大 HSV-1 DNA 改进了 HSV 扩增子载体的辅助病毒包装系统。
DOI：
10.1006/mthe.2001.0294
发表时间：
2001
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy.
影响因子：
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作者：
Saeki,Y;Fraefel,C;Ichikawa,T;Breakefield,XO;Chiocca,EA
通讯作者：
Chiocca,EA
无辅助 HSV-1 扩增子在中枢神经系统中引发的先天免疫反应明显较差。
DOI：
10.1016/s1525-0016(02)00036-9
发表时间：
2003
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Olschowka,JohnA;Bowers,WilliamJ;Hurley,SeanD;Mastrangelo,MichaelA;Federoff,HowardJ
通讯作者：
Federoff,HowardJ