Non-integrating lentiviral vectors based on the minimal S/MAR sequence retain transgene expression in dividing cells
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- 作者：Zhen Xu ; Feng Chen ; Lingling Zhang ; Jing Lu ; Peng Xu…
- 关键词：gene transfer ; non ; integrating lentivirus ; scaffold/matrix attachment region (S/MAR) ; episomal vectors
- 刊名：Science China Life Sciences
- 出版年：2016
- 出版时间：October 2016
- 年：2016
- 卷：59
- 期：10
- 页码：1024-1033
- 全文大小：1,552 KB
- 刊物主题：Life Sciences, general;
- 出版者：Springer Berlin Heidelberg
- ISSN：1869-1889
- 卷排序：59
文摘
Safe and efficient gene transfer systems are the basis of gene therapy applications. Non-integrating lentiviral (NIL) vectors are among the most promising candidates for gene transfer tools, because they exhibit high transfer efficiency in both dividing and non-dividing cells and do not present a risk of insertional mutagenesis. However, non-integrating lentiviral vectors cannot introduce stable exogenous gene expression to dividing cells, thereby limiting their application. Here, we report the design of a non-integrating lentiviral vector that contains the minimal scaffold/matrix attachment region (S/MAR) sequence (SNIL), and this SNIL vector is able to retain episomal transgene expression in dividing cells. Using SNIL vectors, we detected the expression of the eGFP gene for 61 days in SNIL-transduced stable CHO cells, either with selection or not. In the NIL group without the S/MAR sequence, however, the transduced cells died under selection for the transient expression of NIL vectors. Furthermore, Southern blot assays demonstrated that the SNIL vectors were retained extrachromosomally in the CHO cells. In conclusion, the minimal S/MAR sequence retained the non-integrating lentiviral vectors in dividing cells, which indicates that SNIL vectors have the potential for use as a gene transfer tool.