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.