ACTIVATION OF MOLONEY MURINE LEUKEMIA-VIRUS LTR ENHANCES THE TITER OFRECOMBINANT RETROVIRUS IN PSI-GRIP PACKAGING CELLS

The critical physiological function of the long terminal repeat in Mol oney 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 expres sion of MoMLV, on their ability to modulate retroviral transcripts in Psi CRIP producing cell lines. Improvement of recombinat retrovirus pr oduction by two Psi CRIP producer cells was tested by using dexamethas one, TPA and sodium butyrate (Na-But) alone or in combination. We demo nstrate that 5 mM Na-But, or 5 mM Na-But plus 1 mu M dexamethasone sig nificantly enhanced viral production. These compounds could induce a 1 0-fold increase in viral production. There was also a good correlation between the increased viral production and the titer measured after t ransduction of NIH 3T3. This improvement is of general interest, since a major goal for gene therapy is the production of high retroviral ti ter for increased transduction efficiency.