Interferon Induction by a 2′‐Modified Double‐Helical RNA, Poly(2′‐azido‐2′‐deoxyinosinic acid) · polycytidylic acid

Although the presence of free 2′‐hydroxyl groups in both strands of a double‐stranded RNA complex has been recognized as one of the major requisites for the interferon‐inducing activity of double‐stranded RNAs, we have found a particular analogue of (I) n · (C) n in which the 2′‐hydroxyls of the purine nucleotide strand were replaced by azido groups, (dIn 3 ) n · (C) n , to be highly effective in inducing interferon. Various other 2′‐azido analogues of (I) n · (C) n and (A) n · (U) n , i.e. (dIn 3 ) n · (br 5 C) n , (I) n · (dCn 3 ) n , (dAn 3 ) n · (U) n , (A) n · (dUn 3 ) n , (dAn 3 ) n · (rT) n and (dAn 3 ) n · (dUn 3 ) n , were inactive as inducers of interferon. In human fibroblast cultures, the interferon‐inducing activity of (dIn 3 ) n · (C) n equalled that of (I) n · (C) n . In other interferon‐induction systems (primary rabbit kidney cells, mouse L‐929 cells, intact rabbits), (dIn 3 ) n · (C) n was less active than (I) n · (C) n . As assessed by both radio‐chemical and biological means, (dIn 3 ) n · (C) n was more susceptible to degradation by pancreatic ribonuclease and human serum nucleases than was (I) n · (C) n . The t m of (dIn 3 ) n · (C) n was 52.5 °C, as compared to 62.5 °C for (I) n · (C) n , both determined in 0.15 M Na + , pH 7.0. Under the same conditions, (dIn 3 ) n · (br 5 C) n had a t m of 77 °C and (I) n · (br 5 C) n had a t m of 87 °C. The reactivity of (dIn 3 ) n · (C) n and (dIn 3 ) n · (br 5 C) n towards antibodies to double‐stranded RNA was evaluated by quantitative complement fixation, counterimmunoelectrophoresis and competitive radioimmunoassay. In these tests, (dIn 3 ) n · (C) n and (dIn 3 ) n · (br 5 C) n showed an immunoreactivity pattern comparable to that of (I) n · (C) n and (I) n · (br 5 C) n .