Advances in high-capacity extrachromosomal vector technology: episomal maintenance, vector delivery, and transgene expression.
Advances in high-capacity extrachromosomal vector technology: episomal maintenance, vector delivery, and transgene expression.
复制标题
高容量染色体外载体技术的进展：游离维持、载体递送和转基因表达。
DOI：
10.1038/mt.2008.156
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Lufino MM
中科院分区：
文献类型：
--
作者：
Lufino MM
染色体外载体技术的最新发展为设计更安全、生理调节的基因治疗载体提供了新的方法。转导细胞核中染色体外或附加体的持续存在为整合载体提供了一种更安全的替代方案，整合载体在最近的临床试验中发生严重不良事件后已成为安全问题的主题。染色体外载体不会对宿主基因组造成物理破坏，使这些载体成为包括干细胞在内的多种基因治疗靶标的安全且合适的工具。此外，染色体外载体的高插入能力允许从其基因组DNA序列的背景中表达治疗性转基因，提供了表达正常剪接变体并实现生理调节表达水平的优雅方式。在这里，我们描述了几种不同染色体外系统过去和最近的发展进展，讨论了它们的保留机制，并评估了它们作为表达载体传递和表达基因组 DNA 位点的用途。我们还讨论了各种病毒和非病毒递送系统，这些系统已用于在体外和体内将附加型载体递送至靶细胞。最后，我们探索了在干细胞中递送和表达染色体外转基因的潜力。染色体外载体的长期存在与干细胞增殖和分化为多种细胞类型的潜力相结合，为治疗干预提供了令人兴奋的前景。
Recent developments in extrachromosomal vector technology have offered new ways of designing safer, physiologically regulated vectors for gene therapy. Extrachromosomal, or episomal, persistence in the nucleus of transduced cells offers a safer alternative to integrating vectors which have become the subject of safety concerns following serious adverse events in recent clinical trials. Extrachromosomal vectors do not cause physical disruption in the host genome, making these vectors safe and suitable tools for several gene therapy targets, including stem cells. Moreover, the high insert capacity of extrachromosomal vectors allows expression of a therapeutic transgene from the context of its genomic DNA sequence, providing an elegant way to express normal splice variants and achieve physiologically regulated levels of expression. Here, we describe past and recent advances in the development of several different extrachromosomal systems, discuss their retention mechanisms, and evaluate their use as expression vectors to deliver and express genomic DNA loci. We also discuss a variety of delivery systems, viral and nonviral, which have been used to deliver episomal vectors to target cellsin vitroandin vivo.Finally, we explore the potential for the delivery and expression of extrachromosomal transgenes in stem cells. The long-term persistence of extrachromosomal vectors combined with the potential for stem cell proliferation and differentiation into a wide range of cell types offers an exciting prospect for therapeutic interventions.
登录
查看更多内容
转基因小鼠中克隆的成年β-珠蛋白基因的发育调控
影响因子：
64.8
作者：
J. Magram;K. Chada;F. Costantini
通讯作者：
F. Costantini
人体细胞中酵母人工染色体的稳定游离维持
影响因子：
5.3
作者：
Kaetrin Simpson;A. McGuigan;Clare Huxley
通讯作者：
Clare Huxley
通过基于 Epstein-Barr 病毒的载体将极其有效的基因转染至淋巴造血细胞系。
DOI：
--
发表时间：
1997
期刊：
JIM - Journal of Immunological Methods
影响因子：
--
作者：
O. Mazda;E. Satoh;K. Yasutomi;J. Imanishi
通讯作者：
J. Imanishi
嵌合小鼠中人类染色体片段的功能表达和种系传递
影响因子：
30.8
作者：
K. Tomizuka;H. Yoshida;H. Uejima;H. Kugoh;Kaoru Sato;A. Ohguma;M. Hayasaka;K. Hanaoka;M. Oshimura;I. Ishida
通讯作者：
I. Ishida
影响因子：
14.9
作者：
Wade-Martins, R;Frampton, J;James, MR
通讯作者：
James, MR