Polyinosinic: polycytidylic

Polynucleotides. Polynucleotides are potent interferon inducers. A mismatched, double-stranded synthetic polyribonucleotide ampligen and the double-stranded acids, polyadenylic-polyuridylic acid and polyinosinic-polycytidylic acids have been widely studied for cancer therapy(ii). Although these materials elicit excellent activity with murine rodents, therapeutic effects are dramatically decreased within primates. 

Dennis JW (1986) Effects of swainsonine and polyinosinic polycytidylic acid on murine tumor cell growth and metastasis. Cancer Res 46 5131-5136... 

As polyinosine-polycytidylic acid failed to enhance killing of Escherichia coli by mouse peritoneal macrophages in vitro, Thalinger and Mandell (1972) suggested that it acted not directly on mononuclear phagocytes. 

Levy, H.B., Law, L.N., and Rabson, A.S., 1969, Inhibition of tumor growth by polyinosinic-polycytidylic acid, Proc Natl Acad Sci USA, 62 357. 

Engel WK, Cuneo RA, Levy HB. (1978) Polyinosinic-polycytidylic acid treatment of neuropathy. Lancet 1, 503-504. 

A synthetic short double-stranded RNA such as Polyinosinic-polycytidylic acid (poly(I)-poly(C)) is widely used as a inducer in interferon production. The presence of DEAE-Dextran in the reaction medium increases the uptake of poly(I)-poly(C) by the cells and also makes the polynucleotide less susceptible to degradation from RNase. In addition, the... 

Uno T, Hirabayashi K, Murai M (2005) The role of IFN regulatory factor-3 in the cytotoxic activity of NS-9, a polyinosinic-polycytidylic acid/cationic liposome complex, against tumor cells. Mol Cancer Ther 4 799-805... 

Polyinosinic polycytidylic acid (Poly I C) - a TLR3 agonist... 

Interferon is a low molecular weight protein, produced by vims-infected cells, that itself induces the formation of a second protein inhibiting the transcriphon of viral mRNA. Interferon is produced by the host cell in response to the vims particle, the viral nucleic and non-viral agents, including synthetic polynucleides such as polyinosinic acid polycytidylic acid (poly I C). There are two types of interferon. 

Lysine-rich proteinoids preferentially interact to form microparticles with polycytidylic acid and polyuridylic acid. On the other hand arginine-rich proteinoids interacts much more readily with polyguanylic acid and polyinosinic acid to form such particles under the same condition57>. Lysine-rich proteinoids had most often shown a preferential precipitation with polyuridylic acid in the experiments for interaction between polynucleotides and the proteinoids in the presence of Mg2+ 56). 

Figure 22 represents the depolymerization by zinc ions of RNA molecules and other polyribonucleotides, in which all of the bases are the same—i.e., polyadenylic, polycytidylic, polyuridylic, and polyinosinic acid 12). Notice that the rates of degradation, or depolymerization, are not the same. The ability of the metal ion to cleave a phosphodiester linkage seems to depend on the nature of the base adjacent to that linkage. 

Synthetic polynucleotide complexes have been shown to be effective immune response modulators in animals and man (Braun et al. 1971, Johnson 1979). The polynucleotides are formed foUowing the action of an enzyme, polynucleotide phosphor-ylase on the synthetic mononucleotide diphosphates. Complexing takes place following the mixing of polymers composed of opposite base pairs. Two have been utilised, polyinosinic acid complexed with polycytidylic acid (poly I poly C) and polyad-enylic acid complexed with polyuridylic acid (poly A poly U). The single strands mononucleotides are ineffective. 

Anari MR, Cribb AE and Renton KW (1995). The duration of induction and species influences the downregulation of cytochrome P450 by the interferon inducer polyinosinic acid-polycytidylic acid. Drug Metabolism and Disposition, 23 536-41. 

Davies, D. R., Rich, A. The formation of a helical complex between polyinosinic acid and polycytidylic acid. J. Amer. chem. Soc. 80, 1003-1004 (1958). 

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