Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells

S. F. Yu, T. von Ruden, P. W. Kantoff, C. Garber, M. Seiberg, U. Rüther, W. F. Anderson, E. F. Wagner, E. Gilboa

Research output: Contribution to journalArticle

370 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3194-3198
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number10
DOIs
StatePublished - 1986

ASJC Scopus subject areas

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