The use of recombinant retroviruses was pioneered by Richard Mulligan and David Baltimore with the Psi-2 lines and analogous retrovirus packaging systems, based on NIH 3T3 cells (10, 11). Such helper-defective packaging lines are capable of producing all the necessary trans proteins--gag, pol, and env-- that are required for packaging, processing, reverse transcription, and integration of recombinant genomes. Those RNA molecules that have in cis the Psi packaging signal are packaged into maturing virions.