Journal of Biotechnology, 22 (1992) 283-290 283 © 1992 Elsevier Science Publishers B.V. All rights reserved 0168-1656/92/$05.00 BIOTEC 00703 A CHO strain producing high-level human IL-6 with the 3' deletion construct Naoto Tonouchi, Naoto Koyama and Kiyoshi Miwa Central Research Laboratories, Ajinomoto Co. Inc., Kawasaki, Japan (Received 30 June 1991; revisionaccepted 1 August 1991) Summary A Chinese Hamster Ovary (CHO) strain producing high-level human inter- leukin 6 (IL-6) was obtained, by introduction of the IL-6 cDNA from which the 3' AU-rich region was deleted. The IL-6 mRNA of this strain was stable. The productivity was more than 15 times higher than the previously obtained clone, which has intact IL-6 cDNA in the same expression vector. This strain produced IL-6 at a high level of 30/xg m1-1 in batch culture, or a continuous 20 #g per 106 ceils per day in microcarrier cultivation. IL-6 production; CHO cells; 3' AU-rich sequence; Continuous cell culture Introduction AU-rich sequences are widely observed in the 3' untranslated region of many genes including most lymphokines, interferons and protooncogenes (Shaw and Kamen, 1986; Caput et al, 1986). It is known to be a mRNA destabilizing signal through release of the p'oly (A) tail of the mRNA (Brewer and Ross, 1988; Wilson and Treisman, 1988), and this sequence seems to prevent efficient lymphokine production. IL-6, originally identified as B cell stimulatory factor-2 (BSF-2), is a multi-potential cytokine that regulates immune response, an acute phase reaction and hematopoiesis (Kishimoto, 1989), and cDNA cloning (Hirano et al., 1986) has Correspondence to: N. Tonouchi, Central Research Laboratories, Ajinomoto Co. Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki 210, Japan.