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Activation of Moloney murine leukemia virus LTR enhances the titer of recombinant retrovirus in psi CRIP packaging cells.

The critical physiological function of the long terminal repeat in Moloney murine leukemia virus (MoMLV) gene expression has been thoroughly explored and shown to include binding sites for ubiquitous and tissue-specific transcription factors, such as the glucocorticoid responsive element (GRE) and the LVb sequence recognized by phorbol 12-myristate 13-acetate (TPA)-induced factors. The present study was undertaken to determine the effect of different activators, known to enhance expression of MoMLV, on their ability to modulate retroviral transcripts in psi CRIP producing cell lines. Improvement of recombinant retrovirus production by two psi CRIP producer cells was tested by using dexamethasone, TPA and sodium butyrate (Na-But) alone or in combination. We demonstrate that 5 mM Na-But, or 5 mM Na-But plus 1 microM dexamethasone significantly enhanced viral production. These compounds could induce a 10-fold increase in viral production. There was also a good correlation between the increased viral production and the titer measured after transduction of NIH 3T3. This improvement is of general interest, since a major goal for gene therapy is the production of high retroviral titer for increased transduction efficiency.