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Studies on the Toxicity and Antiviral Activity of Various Polynucleotides1
Abstract
Various polynucleotides were examined for antiviral activity and toxicity in mice. Although the antiviral potency of the various interferon inducers varied, there was a concomitant variation in toxicity. This was reflected by a fivefold range in therapeutic ratio for the various compounds. In addition, no polynucleotide proved to be a more potent interferon inducer than polyinosinic·polycytidylic acid [(poly rI)·(poly rC)]. Our results suggest that there may be intrinsic limitations to the development of polynucleotide interferon inducers having improved therapeutic ratios.
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Selected References
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- Absher M, Stinebring WR. Toxic properties of a synthetic double-stranded RNA. Endotoxin-like properties of poly I. poly C, an interferon stimulator. Nature. 1969 Aug 16;223(5207):715–717. [PubMed] [Google Scholar]
- Black DR, Eckstein F, Hobbs JB, Sternbach H, Merigan TC. The antiviral activity of certain thiophosphate and 2'-chloro substituted polynucleotide homopolymer duplexes. Virology. 1972 May;48(2):537–545. [PubMed] [Google Scholar]
- Black DR, Knight CA. Ribonucleic acid transcriptase acitvity in purified wound tumor virus. J Virol. 1970 Aug;6(2):194–198. [PMC free article] [PubMed] [Google Scholar]
- De Clercq E, Eckstein E, Merigan TC. [Interferon induction increased through chemical modification of a synthetic polyribonucleotide]. Science. 1969 Sep 12;165(3898):1137–1139. [PubMed] [Google Scholar]
- CDe Clercq E, Eckstein F, Sternbach H, Merigan TC. The antiviral activity of thiophosphate-substituted polyribonucleotides in vitro and in vivo. Virology. 1970 Oct;42(2):421–428. [PubMed] [Google Scholar]
- De Clercq E, Nuwer MR, Merigan TC. The role of interferon in the protective effect of a synthetic double-stranded polyribonucleotide against intranasal vesicular stomatitis virus challenge in mice. J Clin Invest. 1970 Aug;49(8):1565–1577. [PMC free article] [PubMed] [Google Scholar]
- Field AK, Tytell AA, Lampson GP, Hilleman MR. Inducers of interferon and host resistance. II. Multistranded synthetic polynucleotide complexes. Proc Natl Acad Sci U S A. 1967 Sep;58(3):1004–1010. [PMC free article] [PubMed] [Google Scholar]
- Hobbs J, Sternbach H, Eckstein F. Poly 2'-deoxy-2'-chlorouridylic and -cytidylic acids. FEBS Lett. 1971 Jul 8;15(5):345–348. [PubMed] [Google Scholar]
- Lampson GP, Field AK, Tytell AA, Nemes MM, Hilleman MR. Relationship of molecular size of rIn:rCn (poly I:C) to induction of interferon and host resistance. Proc Soc Exp Biol Med. 1970 Dec;135(3):911–916. [PubMed] [Google Scholar]
- Lindahl-Magnusson P, Leary P, Gresser I. Interferon and cell division. VI. Inhibitory effect of interferon on the multiplication of mouse embryo and mouse kidney cells in primary cultures. Proc Soc Exp Biol Med. 1971 Dec;138(3):1044–1050. [PubMed] [Google Scholar]
- Michelson AM, Monny C. Polynucleotides. X. Oligonucleotides and their association with polynucleotides. Biochim Biophys Acta. 1967 Nov 21;149(1):107–126. [PubMed] [Google Scholar]
- Morahan PS, Munson AE, Regelson W, Commerford SL, Hamilton LD. Antiviral activity and side effects of polyriboinosinic-cytidylic acid complexes as affected by molecular size. Proc Natl Acad Sci U S A. 1972 Apr;69(4):842–846. [PMC free article] [PubMed] [Google Scholar]
- Niblack JF, McCreary MB. Relationship of biological activities of poly I-poly C to homopolymer molecular weights. Nat New Biol. 1971 Sep 8;233(36):52–53. [PubMed] [Google Scholar]
- Tytell AA, Lampson GP, Field AK, Nemes MM, Hilleman MR. Influence of size of individual homopolynucleotides on the physical and biological properties of complexed rIn:rCn (poly I:C). Proc Soc Exp Biol Med. 1970 Dec;135(3):917–921. [PubMed] [Google Scholar]