Non-integrating lentiviral vectors based on the minimal S/MAR sequence retain transgene expression in dividing cells

被引:15
|
作者
Xu, Zhen
Chen, Feng
Zhang, Lingling
Lu, Jing
Xu, Peng
Liu, Guang
Xie, Xuemin
Mu, Wenli
Wang, Yajun
Liu, Depei [1 ]
机构
[1] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Biochem & Mol Biol, State Key Lab Med Mol Biol, Beijing 100005, Peoples R China
关键词
gene transfer; non-integrating lentivirus; scaffold/matrix attachment region (S/MAR); episomal vectors; NONVIRAL EPISOMAL VECTOR; EFFICIENT GENE-TRANSFER; VIRUS TYPE-1 INFECTION; NONDIVIDING CELLS; VIRAL-DNA; IN-VIVO; THERAPY; STABILITY; REPLICATION; PROTEIN;
D O I
10.1007/s11427-016-0067-0
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1024 / 1033
页数:10
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