INCREASING TRANSDUCTION EFFICIENCY OF RECOMBINANT MURINE RETROVIRUS VECTORS BY INITIATION OF ENDOGENOUS REVERSE TRANSCRIPTION - POTENTIAL UTILITY FOR GENETIC THERAPIES

Reverse transcription of retroviral genomic RNA in a target cell is in fluenced by cellular factors, including the concentration of deoxyribo nucleoside triphosphates (dNTPs). In addition, recent data have demons trated that reverse transcription can be driven within human immun:imm unodeficiency virus type 1 virions, prior to infection of a fell, by i ncreasing extracellular concentrations of dNTPs. In attempts to increa se the transduction efficiency of recombinant murine leukemia virus ve ctors, endogenous reverse transcription was initiated within cell-free , recombinant murine leukemia virus virions in the presence of relativ ely high concentrations of dNTPs. As a result, the expression of trans duced genes via these retroviral vectors was increased approximately 1 0-fold by treatment of virions with dNTPs. Combined with our previous data, these observations suggest that virion-associated DNA synthesis can occur in diverse groups of retroviruses and positively alter retro viral infectivity. As such, these manipulations may be useful for incr easing the efficiency of retrovirus-mediated gene delivery.