Anti-cytomegalovirus (CMV) effect of antisense oligodeoxynucleotides phosphorothioates (AS S OND) / 中国药理学通报

ABSTRACT

AIM To study anti CMV effect of S ODNs complementary to the initial code region of major immediate early (MIE) mRNA, and to the intron1/exon2 boundary of MIE mRNA precursor. METHODS To evaluate the anti CMV effect by determining viral antigen on infected 2BS cells by in situ ELISA. RESULTS Both of 2 AS S ODNs and their sense sequence control showed anti CMV effect. The medium effective concentration (EC 50 ) were 4 53, 10 2, 26 2 and 30 1 ?mol?L -1 . The secretion of CMV antigens were delayed by 3 d～4 d by 8 0 ?mol?L -1 AS 1. It showed increased effect by administrating earlier postinfection, by supplementing the S ODN at intervals, by conbinating with ganciclovir, and by packaging with liposome. A slight cytotoxicity was observed at the concentration of 64 0 ?mol?L -1 . Northern blot analysis indicated that the MIE mRNA decreased after the treatment of AS 1. It suggests that disintegration of the mRNA in the hybridized duplex by activated RNase H played an important role as the mechanism of specific action, and "time and effect" analysis suggested that interference of viral adsorbtion and penetration may be the important mechanism of nonspecificity. CONCLUSION AS S ODNs targeted to MIE gene are effective anti CMV agents which can be developed as a new type of chemotherapy drugs against CMV infection.