Effects of sonication on physicochemical and biological properties of synthetic double-stranded polyribonucleotides as interferon inducer

Summary

Two kinds of synthetic double-stranded polyribonucleotides, poly IG∶C¹ and poly I∶:C and their constituent single-stranded polymers were subjected to sonication. Sonication of both poly IG∶C and poly I∶C resulted in decreases in viscosity, molecular size and heterogeneity in the size distribution. In poly IG∶C, whose average sedimentation constant was larger than or around 11 S, these changes were accompanied with enhancements of interferon inducing activity in rabbits and mice and antiviral activity in mice, and moreover with a decrease in the systemic toxicity in mice. In poly I∶C, however, such an enhancement in the interferon inducing activity was observed only when its molecular size corresponded to that of poly IG∶C. Previous sonication of poly C of the relatively large molecular size (> 10 S) has also been shown effective, to a certain extent, in obtaining double-stranded RNA of smaller size distribution with increased interferon inducing activity and lowered toxicity. It has been shown that these changes induced by sonication were based on the breakage of phosphodiester bonds of both double and single-stranded polyribonucleotides. On the basis of the analyses of the correlations between molecular sizes and the biological activities, it has been suggested that, while toxicity decreases always when the molecular size becomes smaller, the optimal size of the double-stranded polyribonucleotide complexes for interferon production ranges roughly from 10 S (9.1×10⁵ daltons) to 5 S (1.2 ×10⁵ daltons).