Double-stranded
polynucleotides, which are composed of two complementary homopolyribonucleotides containing no genetic information, are synthetic molecules capable of mimicking the action of natural
double-stranded RNA or
viral RNA on cells. Double-stranded
polyribonucleotides act as an alarm system alerting the cell to the presence of an external aggression, e.g. a viral attack. In addition,
polyribonucleotides have a more active function in that they trigger cell defense processes through activation of a family of genes, of which some encode
cytokines, activation of cytoplasmic
enzymes involved in
antiviral mechanisms or signal transduction, and activation of nonspecific immune responses. Double-stranded
polyribonucleotides containing one mismatched base pair per helix have been found to be especially interesting. The best known example is
poly(I).poly(C12U), also called
ampligen.
Poly(I).poly(C12U) is capable, in experimental models, of limiting the development of viruses (including HIV), reducing
tumor growth, eliminating
metastases, and, according to one report, preventing steady declines in T-cell counts in HIV-positive patients. Therapeutic doses used in the USA as an experimental
drug induced little toxicity. In vitro,
poly(I).poly(C12U) acts synergistically with
interferon,
interleukin 2 or AZT, suggesting that these latter drugs may be effective in lower, less toxic doses when used in combination with
poly(I).poly(C12U). The therapeutic activity of
poly(I).poly(C12U) holds promise. More extensive prospective studies of this agent are warranted.