[Biological actions and therapeutic perspectives of double stranded polyribonucleotides: a reappraisal].
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.
Thang
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U 245 INSERM, Hôpital Saint-Antoine, Paris, France.
Guschlbauer
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D003586:Cytomegalovirus Infections / Q000628:therapy; D004357:Drug Synergism; D015658:HIV Infections / Q000628:therapy*; D006505:Hepatitis / Q000628:therapy; D006561:Herpes Simplex / Q000628:therapy; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy; D011117:Polyribonucleotide Nucleotidyltransferase / Q000378:metabolism; D011131:Polyribonucleotides / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D012330:RNA, Double-Stranded / Q000235:genetics
D011131:Polyribonucleotides; D012330:RNA, Double-Stranded; D007372:Interferons; D011117:Polyribonucleotide Nucleotidyltransferase
Actions biologiques et perspectives thérapeutiques des polyribonucléotides double-brins: une réévaluation.