SELF-INACTIVATING RETROVIRAL VECTORS DESIGNED FOR TRANSFER OF WHOLE GENES INTO MAMMALIAN-CELLS
SELF-INACTIVATING RETROVIRAL VECTORS DESIGNED FOR TRANSFER OF WHOLE GENES INTO MAMMALIAN-CELLS
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DOI：
10.1073/pnas.83.10.3194
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发表时间：
1986-05-01
影响因子：
11.1
通讯作者：
GILBOA, E
中科院分区：
文献类型：
--
作者：
YU, SF;VONRUDEN, T;GILBOA, E
自失活（SIN）载体是一种逆转录病毒衍生的载体，用于将整个基因转导到哺乳动物细胞中。SIN载体在3“长末端重复（LTR）中含有299个碱基对的缺失，其包括编码增强子和启动子功能的序列。当使用衍生自此类载体的病毒感染NIH 3 T3细胞时，缺失被转移到5“LTR，导致感染细胞中前病毒的转录失活。通过SIN载体将杂交基因（人金属硫蛋白促进的c-fos）引入细胞与重排无关，并导致真实mRNA转录本的形成，在某些情况下，这是由镉诱导的。SIN载体在设计用于研究哺乳动物细胞中基因的调节表达的基因转移实验中应该是特别有用的。在整合的前病毒的两个LTR中缺乏增强子和启动子序列也应该使激活细胞癌基因的可能性最小化，并且可以提供用于人类基因治疗的更安全的替代方案。
A retrovirus-derived vector called self-inactivating (SIN) vector was designed for the transduction of whole genes into mammalian cells. SIN vectors contain a deletion of 299 base pairs in the 3'' long terminal repeat (LTR), which includes sequences encoding the enhancer and promoter functions. When viruses derived from such vectors were used to infect NIH 3T3 cells, the deletion was transferred to the 5'' LTR, resulting in the transcriptional inactivation of the provirus in the infected cell. Introduction of a hybrid gene (human metallothionein-promoted c-fos) into cells via a SIN vector was not associated with rearrangements and led to the formation of an authentic mRNA transcript, which in some cases was induced by cadmium. SIN vectors should be particularly useful in gene transfer experiments designed to study the regulated expression of genes in mammalian cells. Absence of enhancer and promoter sequences in both LTRs of the integrated provirus should also minimize the possibility of activating cellular oncogenes and may provide a safer alternative to be used in human gene therapy.