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Artificial antisense RNAs and recombinant,
trans
-acting ribozymes have been developed whose ability to inhibit gene expression varies from negligible to profound. Although we are only beginning to understand the underlying reasons for this extreme variation, we can identify a number of variables that might well be significant in the process, and some of these can be modeled computationally. It must be emphasized, however, that only well-designed and systematic experimentation will prove whether one or the other of these variables is of key significance in living cells.