IN-VITRO INHIBITION OF MURINE IFN-GAMMA PRODUCTION BY PHOSPHOROTHIOATE DEOXYGUANOSINE OLIGOMERS

Phosphorothioate (PT) oligonucleotides are designed as specific agents for antisense therapy although they have been reported to exert non-s pecific immunomodulatory effects. To elucidate further their actions, the effect of PT deoxyguanosine oligomers (S-oligo(dG)) on in vitro cy tokine production by mouse splenocytes was studied. S-oligo(dG)(20) in hibited production of INF gamma induced by Con A, E. coli DNA or the c ombination of PMA and calcium ionophore A23187. The diester analogue w as inactive, and of PT homo-oligomers tested, S-oligo(dG)(20) was the most active. PT compounds with as few as 5 dG residues could also bloc k INF gamma production. These results indicate that base composition a nd length, as well as the PT backbone, contribute to the inhibition of INF gamma production and extend the range of immunomodulatory effects of PT compounds.