Skip to main content
SpringerLink
Log in

Clinical Antiviral Activities

  • Chapter
Antisense Research and Application

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 131))

Abstract

Development of new antiviral drugs is needed and challenging. Antiviral drug discovery has focused on viral inhibition strategies principally directed at viral penetration and uncoating or viral genome replication, and the era of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) has helped regenerate interest in antiviral drug discovery and development (Table 1). Discovery of many of the active antivirals has been through random drug screening rather than rational drug design (De Clercq et al. 1983;De Clercq 1991). The cellular toxicity due to lack of viral target specificity and the typically short therapeutic half-lives limit the usefulness of many antiviral drugs, including nucleoside analogues. More pharmacologically selective and specific antiviral drugs are needed to help limit toxicity to the host while inhibiting viral replication.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 429.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 549.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Agrawal S (1992) Antisense oligonucleotides as antiviral agents. Trends Biotechnol 10:152–158

    Article  PubMed  CAS  Google Scholar 

  • Agrawal S, Temsamani J (1996) Comparative pharmacokinetics of antisense oligonucleotides. In: Agrawal S (ed) Antisense Therapeutics. Humana, Totowa, NJ, pp 247–270

    Chapter  Google Scholar 

  • Agrawal S, Goodchild J, Civeira MP (1988) Oligodeoxynucleoside phosphoramidates and phosphorothioates as inhibitors of human immunodeficiency virus. Biochemistry 85:7079–7083

    CAS  Google Scholar 

  • Agrawal S, Ikeuchi T, Sun D, Sarin PS, Konopka A, Maizel J, Zamecnik PC (1989) Inhibition of human immunodeficiency virus in early infected and chronically infected cells by antisense oligodeoxynucleotides and their phosphorothioate analogues. Proc Natl Acad Sci USA 86:7790–7794

    Article  PubMed  CAS  Google Scholar 

  • Agrawal S, Temsamani J, Tang JY (1991) Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. Proc Natl Acad Sci USA 88:7595–7599

    Article  PubMed  CAS  Google Scholar 

  • Agrawal S, Temsamani J, Galbraith W, Tang J (1995) Pharmacokinetics of antisense oligonucleotides. Clin Pharmacokinet 28:7–16

    Article  PubMed  CAS  Google Scholar 

  • Akhtar S, Basu S, Wickstrom E, Juliano RL (1991) Interactions of antisense DNA oligonucleotide analogs with phospholipid membranes (liposomes). Nucleic Acids Res 19:5551–5559

    Article  PubMed  CAS  Google Scholar 

  • Anderson KP, Azad RF, Zhang H, Humman J, Miner R, Drew WL (1996a) Growth inhibition of clinical and drug-resistant isolates of human cytomegalovirus by the antisense phosphorothioate oligonucleotide, ISIS 2922. Antiviral Res (submitted)

    Google Scholar 

  • Anderson KP, Fox MC, Brown-Driver V, Martin MJ, Azad RF (1996b) Inhibition of human cytomegalovirus immediate-early gene expression by an antisense oligonucleotide complementary to immediate-early RNA. Antimicrob Agents Chemother 40(9):2004–2011

    CAS  Google Scholar 

  • Andrade M, Scozzari A, Cole DL, Ravikumar VT (1994) Efficient synthesis of antisense oligodeoxyribonucleotide phosphorothioates. Bioorg Med Chem Lett 4(16):2017–2022

    Article  CAS  Google Scholar 

  • Aoki K, Yoshida T, Sugimura T, Terada M (1995) Liposome-mediated in vivo gene transfer of antisense K-ras construct inhibits pancreatic tumor dissemination in the murine peritoneal cavity. Cancer Res 55:3810–3816

    PubMed  CAS  Google Scholar 

  • Azad RF, Driver VB, Tanaka K, Crooke RM, Anderson KP (1993) Antiviral activity of a phosphorothioate oligonucleotide complementary to RNA of the human cytomegalovirus major immediate-early region. Antimicrob Agents Chemother 37(9):1945–1954

    Article  PubMed  CAS  Google Scholar 

  • Azad RF, Brown-Driver VB, Buckheit RW, Anderson KP (1995) Antiviral activity of a phosphorothioate oligonucleotide complementary to human cytomegalovirus RNA when used in combination with antiviral nucleoside analogs. Antiviral Res 28(2):101–111

    Article  PubMed  CAS  Google Scholar 

  • Ballas ZK, Rasmussen WL, Krieg AM (1996) Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J Immunol 157:1840–1845

    PubMed  CAS  Google Scholar 

  • Bennett CF (1995) Intracellular delivery of oligonucleotides with cationic liposomes. In: Akhtar S (ed) Delivery strategies for antisense oligonucleotide therapeutics. CRC Press, Boca Raton, pp 223–232

    Google Scholar 

  • Bennett CF, Chiang M-Y, Chan H, Grimm S (1993) Use of cationic lipids to enhance the biological activity of antisense oligonucleotides. J Liposome Res 3:85–102

    Article  CAS  Google Scholar 

  • Bennett CF, Zuckerman JE et al (1996) Pharmacokinetics in mice of a [3H1-labeled phosphorothioate oligonucleotide formulated in the presence and absence of a cationic lipid. J Control Release 41(1–2):121–130

    Article  CAS  Google Scholar 

  • Bennett CF, Mirejovsky D, Crooke RM, Tsai YJ, Felgner J, Sridhar CN, Wheeler CJ, Felgner PL (1997) Structural requirements for cationic lipid mediated phosphorothioate oligonucleotide delivery to cells in culture. J Drug Target (in press)

    Google Scholar 

  • Black LE, DeGeorge JJ, Cavagnaro JA, Jordan A, Ahn AW (1993) Regulatory considerations for evaluating the pharmacology and toxicology of antisense drugs. Antisense Res Dev 3:399–404

    PubMed  CAS  Google Scholar 

  • Black LE, Farrelly JG, Cavagnaro JA, Ahn CH, DeGeorge JJ, Taylor AS, Defelice AF, Jordan A (1994) Regulatory considerations of oligonucleotide drugs: updated recommendations for pharmacology and toxicology studies. Antisense Res Dev 4:299–301

    PubMed  CAS  Google Scholar 

  • Brandt CR (1991) Evaluation of the efficacy of ISIS 1082 in a murine model of herpes simplex virus ocular infection. Internal report. University of Wisconsin-Madison

    Google Scholar 

  • Brigham KL Schreier H (1993) Cationic liposomes and DNA delivery. J Liposome Res 3:31–49

    Article  Google Scholar 

  • Cantin EM, Podsakoff G, Willey DE, Openshaw H (1992) Antiviral effects of herpes simplex virus specific anti-sense nucleic acids. Adv Exp Med Biol 312:139–150

    Article  PubMed  CAS  Google Scholar 

  • Cheruvallath ZS, Cole DL, Ravikumar VT (1996). Sulfurization efficiency in the solution phase synthesis of deoxyribonucleoside phosphorothioates — comparison of sulfur triethylamine with various sulfurizing agents. Nucleosides Nucleotides 15(9):1441–1445

    Article  CAS  Google Scholar 

  • Cohen JS (1991) Antisense oligodeoxynucleotides as antiviral agents. Antiviral Res 16:121–133

    Article  PubMed  CAS  Google Scholar 

  • Cossum PA, Sasmor H, Dellinger D, Truong L, Cummins L, Owens SR, Markham PM, Shea PJ, Crooke S (1994a) Disposition of the 14C-labeled phosphorothioate oligonucleotide ISIS 2105 after intravenous administration to rats. J Pharmacol Exp Ther 267(3):1181–1190

    Google Scholar 

  • Cossum PA, Truong L, Owen SR, Markham PM, Shea JP, Crooke ST (1994b) Pharmacokinetics of a 14C-labeled phosphorothioate oligonucleotide, ISIS 2105, after intradermal administration to rats. J Pharmacol Exp Ther 269(1):89–94

    CAS  Google Scholar 

  • Coulson JM, Blake NW, Archard LC, Malcolm AD (1992) Antisense oligodeoxynucleotides as antiviral agents. Biochem Soc Trans 20:321S

    PubMed  CAS  Google Scholar 

  • Cowsert LM (1993) Antiviral activities of antisense oligonucleotides. In: Crooke ST, Lebleu B (eds) Antisense research and applications. CRC Press, Boca Raton, pp 521–533

    Google Scholar 

  • Crooke RM (1991) In vitro toxicology and pharmacokinetics of antisense oligonucleotides. Anticancer Drug Des 6:609–646

    PubMed  CAS  Google Scholar 

  • Crooke RM (1993) Cellular uptake, distribution and metabolism of phosphorothioate, phosphodiester, and methylphosphonate oligonucleotides. In: Crooke ST, Lebleu B (eds) Antisense research and applications. CRC Press, Boca Raton. pp 427–449

    Google Scholar 

  • Crooke RM, Hoke GD, Shoemaker JE (1992) In vitro toxicological evaluation of ISIS 1082, a phosphorothioate oligonucleotide inhibitor of herpes simplex virus. Antimicrob Agents Chemother 36:527–532

    Article  PubMed  CAS  Google Scholar 

  • Crooke RM, Graham MJ, Cooke ME, Crooke ST (1995) In vitro pharmacokinetics of phosphorothioate antisense oligonucleotides. J Pharm Exp Ther 275(1):462–473

    CAS  Google Scholar 

  • Crooke ST (1996a) Advances in understanding the pharmacological properties of antisense oligonucleotides. Adv Pharmacol 40:1–49

    Article  Google Scholar 

  • Crooke ST (1996b) Proof of mechanism of antisense drugs. Antisense Nucleic Acid Drug Dev 6(2):145–147

    Article  CAS  Google Scholar 

  • Crooke ST, Bennett CF (1996) Progress in antisense oligonucleotide therapeutics. Annu Rev Pharmacol Toxicol 36:107–129

    Article  PubMed  CAS  Google Scholar 

  • Crooke ST, Grillone LR, Tendolkar A, Garrett A, Fratkin MJ, Leeds J, Barr WH (1994) A pharmacokinetic evaluation of 14C-labeled afovirsen sodium in patients with genital warts. Clin Pharmacol Ther 56:641–646

    Article  PubMed  CAS  Google Scholar 

  • Crooke ST, Graham MJ, Zuckerman JE, Brooks D, Conklin BS, Cummins LL, Greig MJ, Guinosso CJ, Kornbrust D, Manoharan M, Sasmor HM, Schleich T, Tivel KL, Griffey RH (1996) Pharmacokinetic properties of several novel oligonucleotide analogs in mice. J Pharmacol Exp Ther 277(2):923–937

    PubMed  CAS  Google Scholar 

  • Cummins LL, Leeds JM, Greig M, Griffey RH, Graham MJ, Crooke R, Gaus HJ (1996) Capillary gel electrophoresis and mass spectrometry: powerful tools for the analysis of antisense oligonucleotides and their metabolites. XII International roundtable proceedings: nucleosides, nucleotides, and their biological applications (“Making drugs out of nucleosides and oligonucleotides”). La Jolla, CA, 15–19 September 1996

    Google Scholar 

  • De Benedetti AB, Pytel A, Baglioni C (1987) Loss of (2’-5’)oligoadenylate synthetase activity by production of antisense RNA results in lack of protection by interferon from viral infections. Proc Natl Acad Sci USA 84:658–662

    Article  PubMed  Google Scholar 

  • De Clercq E (1991) Targets and strategies for the antiviral chemotherapy of AIDS. TIPS 11:198–205

    Google Scholar 

  • De Clercq E, Descamps J, Balzarini J, Giziewicz J, Barr PJ, Robins MJ (1983) Nucleic acid related compounds. 40. Synthesis and biological activities of 5-alkynyluracil nucleosides. J Med Chem 26:661–666

    Article  PubMed  Google Scholar 

  • Desatnik R, Foster RE, Lowder CY (1996) Treatment of clinically resistant cytomegalovirus retinitis with combined intravitreal injections of ganciclovir and foscarnet. Am J Ophthalmol 122(1):121–123

    PubMed  CAS  Google Scholar 

  • Dewanjee MK, Kapadvanjwala M, Krishan A, Serafini AN, Ghafouripour AK, Oates EL, Lopez DM, Sfakianakis GN (1993) Radiolabeled antisense oligodeoxynucleotides: In vitro and in vivo applications. J Clin Immunoassay 16:276–289

    Google Scholar 

  • Baglioni CY, Foster RE, Avery RK, Prayson RA (1996) Serous retinal detachments in a patient with clinically resistant cytomegalovirus retinitis. Arch Ophthalmol 114(7): 896–897

    Article  Google Scholar 

  • Dunn JP, MacCumber MW, Forman MS, Charache P, Apuzzo L, Jabs DA (1995) Viral sensitivity testing in patients with cytomegalovirus retinitis clinically resistant to foscarnet or ganciclovir. Am J Ophthalmol 119(5):587–596

    PubMed  CAS  Google Scholar 

  • Fisher TL, Terhorst T, Cao X, Wagner RW (1993) Intracellular disposition and metabolism of fluorescently-labeled unmodified and modified oligonucleotides miroinjected into mammalian cells. Nucleic Acids Res 21(16):3857–3865

    Article  PubMed  CAS  Google Scholar 

  • Gao W-Y, Stein CA, Cohen JS, Dutschman GE, Cheng YC (1989) Effect of phosphorothioate homo-oligodeoxynucleotides on herpes simplex virus type 2-induced DNA polymerase. J Biol Chem 264:11521–11526

    PubMed  CAS  Google Scholar 

  • Gao W-Y, Hanes RN, Vasquez-Padua MA, Stein CA, Cohen JS, Cheng YC (1990a) Inhibition of herpes simplex virus type 2 growth by phosphorothioate oligodeoxynucleotides. Antimicrob Agents Chemother 34:808–812

    Article  CAS  Google Scholar 

  • Gao W-Y, Jaroszewski JW, Cohen JS, Cheng YC (1990b) Mechanisms of inhibition of herpes simplex virus type 2 growth by 28-mer phosphorothioate oligodeoxycytidine. J Biol Chem 265(33):20172

    CAS  Google Scholar 

  • Geary RS, Leeds JM, Shanahan W, Glover J, Pribble J, Truong L, Fitchett J, Burckin T, Nicklin P, Philips J, Levin AA (1996) Sequence independent plasma and tissue kinetics for three antisense phosphorothioate oligonucleotides: mouse to man. American association of pharmaceutical sciences meeting, Seattle, WA, 27–31 October 1996

    Google Scholar 

  • Glover JM, Leeds JM, Mant TGK, Amin D, Kisner DL, Zuckerman J, Geary RS, Levin AA, Shanahan WR (1997) Phase 1 safety and pharmacokinetic profile of an ICAM-1 antisense oligodeoxynucleotide (ISIS 2302). J Pharmacol Exp Ther (in press)

    Google Scholar 

  • Goodchild J, Agrawal S, Civeira MP, Sarin PS, Sun D, Zamecnik PC (1988) Inhibition of human immunodeficiency virus replication by antisense oligodeoxynucleotides [published erratum appears in Proc Natl Acad Sci USA 1989 Mar; 86(5):1504]. Proc Natl Acad Sci U S A 85:5507–5511

    Google Scholar 

  • Hoke GD, Draper K, Freier S, Gonzalez C, Driver VB, Zounes MC, Ecker DJ (1991) Effects of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral efficacy versus herpes simplex virus infection. Nucleic Acids Res 19(20):5743–5748

    Article  PubMed  CAS  Google Scholar 

  • Hsiung GD, Chan VF (1989) Evaluation of new antiviral agents. II. The use of animal models. Antiviral Res 12:239–258

    Article  PubMed  CAS  Google Scholar 

  • Hughes JA, Avrutskaya AV, Brouwer KL, Wickstrom E, Juliana RL (1995) Radiolabeling of methylphosphonate and phosphorothioate oligonucleotides and evaluation of their transport in everted rat jejunum sacs. Pharm Res 12:817–824

    Article  PubMed  CAS  Google Scholar 

  • Iversen PL, Mata J, Tracewell WG, Zon G (1994) Pharmacokinetics of an antisense phosphorothioate oligodeoxynucleotide against rev from human immunodeficiency virus type 1 in the adult male rat following single injections and continuous infusion. Antisense Res Dev 4:43–52

    PubMed  CAS  Google Scholar 

  • Jabs DA (1995) Ocular manifestations of HIV infection. Trans Am Ophthalmol Soc 93(83):623–683

    PubMed  CAS  Google Scholar 

  • Jabs DA, Dunn JP, Enger C, Forman M, Bressler N, Charache P (1996) Cytomegalovirus retinitis and viral resistance. Prevalence of resistance at diagnosis, 1994. Cytomegalovirus Retinitis and Viral Resistance Study Group. Arch Ophthalmol 114(7):809–814

    Article  PubMed  CAS  Google Scholar 

  • Jacob A, Duval-Valentin G, Ingrand D, Thuong NT, Helene C (1993) Inhibition of viral growth by an a-oligonucleotide directed to the splice junction of herpes simplex virus type-1 immediate-early pre-mRNA species 22 and 47. Eur J Biochem 216:19–24

    Article  PubMed  CAS  Google Scholar 

  • Juliano RL, Akhtar S (1992) Liposomes as a drug delivery system for antisense oligonucleotides. Antisense Res Dev 2:165–176

    PubMed  CAS  Google Scholar 

  • Klinman DM, AE-Kyung Y, Yi AK, Beaucage SL, Conover J, Krieg AM (1996) CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon x. Proc Natl Acad Sci USA 93:2879–2883

    Article  PubMed  CAS  Google Scholar 

  • Krieg AM, Yi A-K, Matson S, Waldschmidt TJ, Koretzky GA, Klinman DM (1995) CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374:546–549

    Article  PubMed  CAS  Google Scholar 

  • Krotz AH, Klopchin P, Cole DL, Ravikumar VT (1997) Phosphorothioate oligonucleotides: largely reduced (n-1)-mer and phosphodiester content through the use of dimeric phosphoramidite synthons. Bioorg Med Chem Lett 7(1):73–78

    Article  CAS  Google Scholar 

  • Kulka M, Smith. CC, Aurelian L, Fishelevich R, Meade K, Miller P, Ts’o POP (1989) Site specificity of the inhibitory effects of oligo(nucleoside methylphosphonate)s complementary to the acceptor splice junction of herpes simplex virus type 1 immediate early mRNA 4. Proc Natl Acad Sci USA 86:6868–6872

    Article  PubMed  CAS  Google Scholar 

  • Kulka M, Wachsman M, Miura S, Fishelevich R, Miller PS, Ts’o POP, Aurelian L (1993) Antiviral effect of oligo(nucleoside methylphosphonates) complementary to the herpes simplex virus type 1 immediate early mRNAs 4 and 5. Antiviral Res 20:115–130

    Article  PubMed  CAS  Google Scholar 

  • Lappalainen K, Urtti A, Jaaskelainen I, Syrjanen K, Syrjanen S (1994) Cationic liposomes mediated delivery of antisense oligonucleotides targeted to HPV 16 E7 mRNA in CaSki cells. Antiviral Res 23:119–130

    Article  PubMed  CAS  Google Scholar 

  • Leeds JM, Graham M, Truong L, Cummins LL (1996) Quantitation of phosphorothioate oligonucleotides in human plasma. Anal Biochem 235:36–43

    Article  PubMed  CAS  Google Scholar 

  • Leeds JM, Kornbrust D, Truong L, Henry S (1994) Metabolism and pharmacokinetic analysis of a phosphorothioate oligonucleotide after intravitreal injection. American association of pharmaceutical sciences meeting, 9th annual meeting, San Diego, CA, 6–10 November 1994 [Abstr in Pharm Res 11(10):S35–37

    Google Scholar 

  • Leiter JME, Agrawal S, Palesc P, Zamecnik PC (1990) Inhibition of influenza virus replication by phosphorothioate oligodeoxynucleotides. Proc Natl Acad Sci USA 87:3430–3434

    Article  PubMed  CAS  Google Scholar 

  • Letsinger RL, Zhang GR, Sun DK, Ikeuchi T, Sarin PS (1989) Cholesteryl-conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture. Proc Natl Acad Sci USA 86:6553–6556

    Article  PubMed  CAS  Google Scholar 

  • Litzinger DC, Brown JM, Wala I, Kaufman SA, Van GY, Farrell CL, Collins D (1996) Fate of cationic liposomes and their complex with oligonucleotide in vivo. Biochem Biophy Acta 1281:139–149

    Article  Google Scholar 

  • Luster MI, Portier C, Pait DG, White KL Jr, Gennings C, Munson AE, Rosenthal GJ (1992) Risk assessment in immunotoxicology. Fundam Appl Toxicol 18:200–210

    Article  PubMed  CAS  Google Scholar 

  • Luster MI, Munson AE, Thomas PT, Holsapple MP, Fenters JD, White KL Jr, Lauer LD, Germolec DR, Rosenthal GJ, Dean JH (1988) Development of a testing battery to assess chemical-induced immunotoxicity: national toxicology program’s guidelines for immunotoxicity evaluation in mice. Fundam Appl Toxicol 10:2–19

    Article  PubMed  CAS  Google Scholar 

  • Mirabelli CK, Crooke ST (1993) Antisense oligonucleotides in the context of modern molecular drug discovery and development. In: Crooke ST, Lebleu B (eds) Antisense research and applications. CRC Press, Boca Raton, pp 7–35

    Google Scholar 

  • Ojwang J, Okleberry KM, Marshall HB, Vu HM, Huffman JH, Rando RF (1994) Inhibition of Friend murine leukemia virus activity by guanosine/thymidine oligonucleotides. Antiviral Res 25:27–41

    Article  PubMed  CAS  Google Scholar 

  • Phillips JA, Craig SJ, Bayley D, Christian RA, Geary R, Nicklin PL (in press) Pharmacokinetics, metabolism and elimination of a 20-mer phosphorothioate oligodeoxynucleotide (CGP 69846A) after intravenous and subcutaneous administration. Biochem Pharmacol

    Google Scholar 

  • Piwnica-Worms D (1994) Making sense out of anti-sense: challenges of imaging gene translation with radiolabeled oligonucleotides. J Nucl Med 35:1064–1066

    PubMed  CAS  Google Scholar 

  • Proudnikov D, Mirzabekov A (1996). Chemical methods of DNA and RNA fluorescent labeling. Nucleic Acids Res 24:4535–4532

    Article  PubMed  CAS  Google Scholar 

  • Ravikumar VT, Andrade M, Wyrzykiewicz, Scozzari A, Cole DL (1995) Large-scale synthesis of oligodeoxyribonucleotide phosphorothioate using controlled-pore glass as support. Nucleosides Nucleotides 14(6):1219

    Article  CAS  Google Scholar 

  • Saijo Y, Perlaky L, Wang H, Busch H (1994) Pharmacokinetics, tissue distribution, and stability of antisense oligodeoxynucleotide phosphorothioate ISIS 3466 in mice. Oncol Res 6:243–249

    PubMed  CAS  Google Scholar 

  • Sands H, Gorey-Feret LJ, Cocuzza AJ, Hobbs FW, Chidester D, Trainor GL (1994) Biodistribution and metabolism of internally 3H-labeled oligonucleotides. I. Comparison of a phosphodiester and phosphorothioate. Mol Pharmacol 45:932–943

    PubMed  CAS  Google Scholar 

  • Sandy CJ, Bloom PA, Graham EM, Ferris JD, Shah SM, Schulenburg WE, Migdal CS (1995) Retinal detachment in AIDS-related cytomegalovirus retinitis. Eye 9 (3):277–281

    Article  PubMed  Google Scholar 

  • Sanghvi YS, Cook PD (1993) Towards second-generation synthetic backbones for antisense oligonucleotides. In: Chu CK, Baker DC (eds) Nucleosides, nucleotides as antiviral and antitumor agents. Plenum, New York, pp 309–322

    Google Scholar 

  • Sarin PS, Agrawal S, Civeira MP, Goodchild J, Ikeuchi T, Zamecnik PC (1988) Inhibition of acquired immunodeficiency syndrome virus by oligodeoxynucleoside methylphosphonates. Proc Natl Acad Sci USA 85:7448–7451.

    Article  PubMed  CAS  Google Scholar 

  • Schuette JM, Cole DL, Srivatsa GS (1994) Development and validation of a method for routine base composition analysis of phosphorothioate oligonucleotides. J Pharm Biomed Anal 12:1345–1353

    Article  PubMed  CAS  Google Scholar 

  • Shoji Y, Shimada J, Mizushima Y, Iwasawa A, Nakamura Y, Inouye K, Azuma T, Sakurai M, Nishimura T (1996) Cellular uptake and biological effects of antisense oligodeoxynucleotide analogs targeted to herpes simplex virus. Antimicrob Agents Chemother 40(7):1670–1675

    PubMed  CAS  Google Scholar 

  • Smith CC, Aurelian L, Reddy MP, Miller PS, Ts’o POP (1986) Antiviral effect of an oligo(nucleoside methylphosphonate) complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5. Proc Natl Acad Sci USA 83:2787–2791

    Article  PubMed  CAS  Google Scholar 

  • Srinivasan SK, Iversen P (1995) Review of in vivo pharmacokinetics and toxicology of phosphorothioate oligonucleotides. J Clin Lab Anal 9:129–137

    Article  PubMed  CAS  Google Scholar 

  • Srivatsa GS, Batt M, Schuette J, Carlson RH, Fitchett J, Lee C, Cole DL (1994) Quantitative capillary gel electrophoresis (QCGE) assay of phosphorothioate oligonucleotide in pharmaceutical formulations. J Chromatogr 680:469–477

    Article  CAS  Google Scholar 

  • Stein CA (1992) Anti-sense oligodeoxynucleotides — promises and pitfalls. Leukemia 6:967–974

    PubMed  CAS  Google Scholar 

  • Stein CA (1995) Does antisense exist? Nat Med 1(11):1119–1121

    Article  PubMed  CAS  Google Scholar 

  • Stein CA (1996) Phosphorothioate antisense oligodeoxynucleotides: questions of specificity. TIBTECH 14:147–149

    Article  CAS  Google Scholar 

  • Stein CA, Cheng YC (1993) Antisense oligonucleotides as therapeutic agents — is the bullet really magical? Science 261(5124):1004–1012

    Article  PubMed  CAS  Google Scholar 

  • Stein CA, Krieg AM (1994) Problems in interpretation of data derived from in vitro and in vivo use of antisense oligodeoxynucleotides. Antisense Res Dev 4:67–69

    PubMed  CAS  Google Scholar 

  • Stein CA, Tonkinson JL, Yakubov L (1991) Phosphorothioate oligodeoxynucleotides — antisense inhibitors of gene expression? Pharmacol Ther 52:365–384

    Article  PubMed  CAS  Google Scholar 

  • Takayama S, Hayashi Y (1993) The establishment of international guidelines for reproductive an developmental toxicity studies. Appl Clin Trials 2(9):28–35

    Google Scholar 

  • Urdea MS, Warner BD, Running JA, Stempien M, Clyne J, Horn T (1988) A comparison of non-radioisotopic hybridization assay methods using fluorescent, chemiluminescent and enzyme labeled synthetic oligodeoxyribonucleotide probes. Nucleic Acids Res 16: 4937–4956

    Article  PubMed  CAS  Google Scholar 

  • Vinogradov SV, Suzdaltseva Y, Alakhov VYu, Kabanov AV (1994) Inhibition of herpes simplex virus 1 reproduction with hydrophobized antisense oligonucleotides. Biochem Biophys Res Commun 203:959–966

    Article  PubMed  CAS  Google Scholar 

  • Wallace TL, Bazemore SA, Kornbrust DJ, Cossum PA (1996) Repeat-dose toxicity and pharmacokinetics of a partial phosphorothioate anti-HIV oligonucleotide (AR177) after bolus intravenous administration to cynomolgus monkeys. J Pharmacol Exp Ther 278(3):1313–1317

    PubMed  CAS  Google Scholar 

  • Wyrzykiewicz TK, Cole DL (1994) Sequencing of oligonucleotide phosphorothioates based on solid-supported desulfurization. Nucleic Acids Res 22:2667–2669

    Article  PubMed  CAS  Google Scholar 

  • Zaia JA, Rossi JJ, Murakawa GJ, Spallone PA, Stephens DA, Kaplan BE, Eritja R, Wallace RB, Cantin EM (1988) Inhibition of human immunodeficiency virus by using an oligonucleoside methylphosphonate targeted to the tat-3 gene. J Virol 62:3914–3917

    PubMed  CAS  Google Scholar 

  • Zamecnik PC, Stephenson ML (1978) Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc Natl Acad Sci USA 75:289–294

    Article  Google Scholar 

  • Zamecnik PC, Goodchild J, Taguchi Y, Sarin PS (1986) Inhibition of replication and expression of human T-cell lymphotropic virus type III in cultured cells by exogenous synthetic oligonucleotides complementary to viral RNA. Proc Natl Acad Sci USA 83:4143–4146

    Article  PubMed  CAS  Google Scholar 

  • Zelphati O, Szoka FC (1996a) Liposomes as a carrier for intracellular delivery of antisense oligonucleotides: A real or magic bullet? J Control Release 41(1/2):99–119

    Article  CAS  Google Scholar 

  • Zelphati O, Szoka FC (1996b) Mechanism of oligonucleotide release from cationic liposomes. Proc Natl Acad Sci USA 93(21):11493–11498

    Article  CAS  Google Scholar 

  • Zelphati O, Imbach JL, Signoret N, Zon G, Rayner B, Leserman L (1994) Antisense oligonucleotides in solution or encapsulated in immunoliposomes inhibit replication of HIV-1 by several different mechanisms. NAR 22:4307–4314

    Article  PubMed  CAS  Google Scholar 

  • Zhang R, Diasio RB, Lu Z, Liu T, Jiang Z, Galbraith WM, Agrawal S (1995a) Pharmacokinetics and tissue distribution in rats of an oligodeoxynucleotide phosphorothioate (GEM 91) developed as a therapeutic agent for human immunodeficiency virus type-1. Biochem Pharmacol 49:929–939

    Article  CAS  Google Scholar 

  • Zhang R, Yan J, Shahinian H, Amin G, Lu Z, Liu T, Saag MS, Jiang Z, Temsamani J, Martin RR et al (1995b) Pharmacokinetics of an anti-human immunodeficiency virus antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects. Clin Pharmacol Ther 58:44–53

    Article  CAS  Google Scholar 

  • Zhang R, Iyer RP, Yu D, Tan W, Zhang X, Lu Z, Zhoa H, Agrawal S (1996) Pharmacokinetics and tissue distribution of a chimeric oligodeoxynucleotide phosphorothioate in rats after intravenous administration. J Pharmacol Exp Ther 278:971–979

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. S. L. Hutcherson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. ISIS Pharmaceuticals, Inc., Carlsbad Research Center, 2292 Faraday Avenue, Carlsbad, CA, 92008, USA

    Stanley T. Crooke M.D., Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hutcherson, S.L. (1998). Clinical Antiviral Activities. In: Crooke, S.T. (eds) Antisense Research and Application. Handbook of Experimental Pharmacology, vol 131. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58785-6_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-58785-6_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63730-8

  • Online ISBN: 978-3-642-58785-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation