Use of anti-sense sequences to increase responsiveness to gene amplification

This application is a 371 of PCT/US95/15098, filed Nov. 27, 1995. A method for regulating the production level of a desired protein in a transformed mammalian cell, comprising: a directly amplifiable gene sequence, in expressable form, which when expressed renders said cell more resistant to a toxic agent; a gene of interest, in expressible form, which encodes a desired protein foreign to said cell; and an anti-sense gene sequence, in transcribable form, encoding an anti-sense RNA capable of selectively hybridizing to at least a portion of the mRNA transcribed from said directly amplifiable gene sequence so as to inhibit the translation of said mRNA, such that a higher level of amplification of said directly amplifiable gene and said gene of interest can be achieved, if the cell is exposed to a sufficient level of the toxic agent, that in the absence of said anti-sense RNA.