Diminishing viral gene expression by promoter replacement

Chemistry: molecular biology and microbiology – Process of mutation – cell fusion – or genetic modification – Introduction of a polynucleotide molecule into or...

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4353201, 536 231, 536 235, 536 237, 536 2372, 536 241, C12N 1564, C12N 1534, C12N 1512

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061107441

ABSTRACT:
The present invention provides viral vectors that have been engineered to contain a synthetic promoter that controls at least one essential gene. The synthetic promoter is induced by a specific gene product not normally produced in the cells in which the viral vector is to be transferred. The vectors are propagated in producer or helper cells that express the inducing factor, thereby permitting the virus to replicate to high titer. The lack of the inducing factor in the target cells precludes viral replication, however, meaning that no vector toxicity or immunogenicity arises. Where the virus carries a gene of interest, this should provide for higher level expression for longer periods of time than with current vectors. Methods for making the vectors, helper cells, and their use in protein production, vaccines and gene therapy are disclosed.

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