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Any method known to those of skill in the art may be used to introduce nucleotide substitutions into the coding sequence of gene encoding a tetracycline repressor protein to create the pool of mutated repressors or portions thereof comprising at least one substitution including, but not limited to, spontaneous mutations, error-prone PCR (Leung et al., (1989) Technique 1: 11-15), chemical mutagenesis (Eckert et al., Mutat..

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