Many attempts have been made to inhibit viral and neoplastic diseases by targeting the RNA system. The pathophysiologic significance of the microRNA system and the therapeutic potential of its manipulation are discussed. Studies of double-stranded RNA derivatives are reviewed. The therapeutic potential of one of these compounds, polyl: MPC, is emphasized. Studies of other related antiviral and antineoplastic agents are discussed, including 2′-deoxyoligocytidilates and telomerase inhibitors.
HeL, ThompsonJM, HemannMT, Hemando-MangeE, MuD, GoodsonS, PowersS. A microRNA polycistron as potential human oncogene. Nature435: 828–833, 2005.
4.
MeltzerPS. Cancer genomics: small RNAs with big impacts [news]. Nature435: 745–746, 2005.
5.
HamptonT. MicroRNAs move into cancer research [news]. JAMA294: 411–412, 2005.
6.
BartelDP. MicroRNAs: genetics, biogenesis, mechanism, and function. Cell116: 281–297, 2004.
7.
OtaA, TagawaH, KarnanS, TsuzukiS, KarpasA, KiraS, YoshidaY, SetoM. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res64: 3087–3095, 2004.
8.
JohnsonSM, GrosshansH, ShingaraJ, ByromM, JarvisR, ChengA, LabourierE, ReinertKL, BrownD, SlackFJ. RAS is regulated by the let-7 microRNA family. Cell120: 635–647, 2005.
9.
MichaelMZ, O'connorSM, van Holst PellekaanNG, YoungGP, JamesRJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res1: 882–891, 2003.
10.
GinsbergD. E2F1 pathways to apoptosis. FEBS Lett529: 122–125, 2002.
TorrencePF, DeClereqE. Interferon inducers: general surgery and classification. Methods Enzymol78: 291–299, 1981.
13.
DeClereqE. Synthetic interferon inducers. Top Curr Chem52: 173–203, 1974.
14.
SenGC, TairaH, LengyelP. Interferon, double-stranded RNA, and protein phosphorylation: characteristics of a double-stranded RNA-activated protein kinase system partially purified from interferon treated Ehrlich ascites tumor cells. J Biol Chem253: 5915–5921, 1978.
15.
LevyHB. Interferon and interferon inducers, I: the treatment of malignancies. Arch Intern Med126: 78–83, 1970.
16.
LevyHB, LawLW, RabsonAS. Inhibition of tumor growth by polyinosinic-polycytidylic acid. Proc Natl Acad Sci U S A62: 357–361, 1969.
17.
BucurN, MizunoM, WakabayashiT, YoshidaJ. Growth inhibition of experimental glioma by human interferon-β superinduced by cationic liposomes entrapping polyinosilic:polycytidylic acid. Neurol Med Chir (Tokyo)38: 469–474, 1998.
18.
StebbingN, GranthamCA. Anti-viral activity against encephalomyocarditis virus and Semliki Forest virus and acute toxicity of poly I and poly C administered sequentially to mice. Arch Virol51: 199–215, 1976.
19.
BardosTJ, AradiJ, HoYK, HalmanTI. Biochemical properties of 5-sulfur-substituted pyrimidine nucleosides and nucleotides. Ann N Y Acad Sci255: 522–531, 1975.
20.
BardosTJ, NovakP, ChakrabatiP, HoYK. Partially thiolated polycytidylic acid. In: TownsendLB, TipsonRS, Eds. Nucleic Acid Chemistry. New York: J Wiley & Sons Inc. pp 881–884, 1978.
BardosTJ, SchinaziRF, LingKH, HelderAR. Structure-activity relationships and mode of action of 5-mercapto-substituted oligo- and polynucleotides as antitemplates inhibiting replication of human immunodeficiency virus type 1. Antimicrob Agents Chemother36: 108–114, 1992.
24.
CavanaughPFJr., HoYK, HughesRGJr, BardosTJ. Selectivity of antitemplates as inhibitors of deoxyribonucleic acid polymerases. Biochem Pharmacol31: 4055–4060, 1982.
25.
ChadhaKC, DembinskiWE, DunnCB, AradiJ, BardosTJ, DunnJA, AmbrusJLSr. Effect of increasing thiolation of the polycytidylic acid strand of poly I:poly C on the α, β and γ interferon-inducing properties, antiviral and antiproliferative activities. Antiviral Res64: 171–177, 2004.
26.
KungMP, HoYK, BardosTJ. Action of partially thiolated polynucleotides on the DNA polymerase alpha from regenerating rat liver. Cancer Res36: 4537–4542, 1976.
27.
HeiderAR, BardosTJ. Oligonucleotides and polynucleotides as potential cancer chemotherapeutic agents. In: FoyeWO, Ed. Cancer Chemotherapeutic Agents. Washington:American Chemical Society, pp 526–575, 1996.
28.
MilkulskiAJ, BardosTJ, ChakrabartiP, KalmanTI, ZsindelyA. Inhibition of DNA-dependent RNA polymerase with partially thiolated polynucleotides. Biochem Biophys Acta319: 294–303, 1973.
29.
HorvathA, AradiJ. Advantages of sodium perchlorate solution as mobile phase for purification of synthetic oligonucleotides by anion exchange chromatography. Anal Biochem338: 341–343, 2005.
30.
ChadhaKC, StadlerI, AmbrusJL, NairMPN. Effect of alcohol and MAIDS virus infection upon immunological status in C57BL/6 mice. Recent Res Dev Immunol2: 41–51, 2000.
31.
StadlerI, ChadhaKC, NakeebS, ToumbisC, ButschJ, MathurN, MunschauerF, VladutiuA, SatchidanandSK, AmbrusJL. Pentoxifylline and meclofenamic acid treatment reduces clinical manifestations in a murine model of AIDS. J Pharmacol Exp Ther268: 10–13, 1994.
32.
ChadhaKC, AmbrusJLJr, DembinskiW, AmbrusJLSr.. Interferons and interferon inhibitory activity in disease and therapy. Exp Biol Med229: 285–290, 2004.
33.
TokesS, AradiJ. (s4dU)35: A novel, highly potent oligonucleotide inhibitor of the human immunodeficiency virus type 1 reverse transcriptase. FEBS Lett396: 43–46, 1996.
SzatmariI, TokesS, DunnC, BardosTJ, AradiJ. Modified telomeric repeat amplification protocol: a quantitative radioactive assay for telomerase without using electrophoresis. Anal Biochem282: 80–88, 2000.
36.
TarkanyiI, HorvathA, SzatmariI, EizertH, VamosiG, DamjanovichS, Segal-BendirdjianE, AradiJ. Inhibition of human telomerase by oligonucleotide chimeras, composed of an antisense moiety and a chemically modified homo-oligonucleotide. FEBS Lett579: 1411–1416, 2005.
37.
MorinGB. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell59: 521–529, 1989.
38.
KelleherC, TeixeiraMT, ForstemannK, LingnerJ. Telomerase: biochemical considerations for enzyme and substrate, Trends Biochem Sci27:572–579, 2002.
39.
KimNW, PiatyszekMA, ProwseKR, HarleyCB, WestMD, HoPLC, CovieloGM, WrightWE, WeinrichSL, ShayJW. Specific association of human telomerase activity with immortal cells and cancer. Science266: 2011–2015, 1994.
40.
StewartSA, HahnWC, O'connorBF, BannerEN, LundbergAS, ModhaP, MizunoH, BrooksMW, FlemingM, ZimonjicDB, PopescuNC, WeinbergRA. Telomerase contributes to tumorigenesis by a telomere length-independent mechanism. Proc Natl Acad Sci U S A99: 12606–12611, 2002.
41.
MergnyJL, RiouJF, MaillietP, Teulade-FichouMP, GilsonE. Natural and pharmacological regulation of telomerase. Nucleic Acids Res30: 839–865, 2002.
42.
MatthesE, LehmannC. Telomerase protein rather than its RNA is the target of phosphorothioate-modified oligonucleotides. Nucleic Acids Res27: 1152–1158, 1999.