Antisense Oligonucleotide Therapies: Are They the “Magic Bullets”?
Authors: David D. F. Ma
Journal: Annals of Internal Medicine (1994)

Editorials15 January 1994Antisense Oligonucleotide Therapies: Are They the "Magic Bullets"?David D. F. Ma, MBBS, MD and Trung Le Doan, PhDDavid D. F. Ma, MBBS, MDThe Royal North Shore Hospital, Sydney, NSW, Australia 2065. Museum National d'Histoire Naturelle, 75231 Paris, France. and Trung Le Doan, PhDThe Royal North Shore Hospital, Sydney, NSW, Australia 2065. Museum National d'Histoire Naturelle, 75231 Paris, France.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-2-199401150-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The recent commencement of clinical trials using antisense oligonucleotide therapy for leukemias and viral infections has heralded a new era in drug therapy [1-4]. Antisense oligonucleotides are short chains of nucleic acids, usually 10 to 30 residues long, and are intermediate in size compared with smaller-size conventional drugs, such as β-blockers, and the much larger therapeutic polypeptides, such as growth factors or monoclonal antibodies. Conventional drugs generally affect cellular functions by interacting with proteins.Despite substantial advances in the understanding of molecular interactions between proteins and their ligands, it is difficult to design drugs based on the amino acid sequences ...References1. Uhlmann E, Peyman A. Antisense oligonucleotides: A new therapeutic principle. Chemical Review. 1990; 90:544-83. Google Scholar2. Zon G. Pharmaceutical considerations. In: Cohen JS, ed. Oligodeoxynucleotides: Antisense Inhibitors of Gene Expression. London: Macmillan; 1989:233-47. Google Scholar3. Helene C, Toulme JJ. Specific regulation of gene expression by antisense, sense and antigene nucleic acids. Biochem Biophys Acta. 1990; 1049:99-125. Google Scholar4. Le Doan T, Chavany C, Helene C. Antisense oligonucleotides as potential antiviral and anticancer agents. Bull Cancer. 1989; 76:849-52. Google Scholar5. Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, et al. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science. 1993; 259:1745-9. Google Scholar6. Wickstrom E. Strategies for administering targeted therapeutic oligodeoxynucleotides, a review. Trends in Biotechnology. 1992; 10: 281-7. Google Scholar7. Agrawal S. Antisense oligonucleotides as antiviral agents. Trends in Biotechnology. 1992; 10:152-8. Google Scholar8. Zamecnik PC, Stephenson ML. Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligonucleotide. Proc Natl Acad Sci U S A. 1978; 75:280-4. Google Scholar9. Mirabelli CK, Bennett CF, Anderson K, Crooke ST. In vitro and in vivo pharmacologic activities of antisense oligonucleotides. Anticancer Drug Des. 1991; 6:647-61. Google Scholar10. Wu GY, Wu CH. Specific inhibition of hepatitis B viral gene expression in vitro by targeted antisense oligonucleotides. J Biol Chem. 1992; 267:12436-9. Google Scholar11. Lisziewicz J, Sun D, Klotman M, Agrawal S, Zamecnik P, Gallo R. Specific inhibition of human immunodeficiency virus type I replication by antisense oligonucleotides: an in vitro model for treatment. Proc Natl Acad Sci U S A. 1992; 89:11209-13. Google Scholar12. Cowsert LM, Fox MC, Zon G, Mirabelli CK. In vitro evaluation of phosphorothioate oligonucleotides targeted to the E2 mRNA of papillomavirus: potential treatment for genital warts. Antimicrob Agents Chemother. 1993; 37:171-7. Google Scholar13. Rapaport E, Misiura K, Agrawal S, Zamecnik P. Antimalarial activities of oligodeoxynucleotide phosphorothioates in chloroquine-resistant Plasmodium falciparum. Proc Natl Acad Sci U S A. 1992; 89:8577-80. Google Scholar14. Helene C. Rational design of sequence-specific oncogene inhibitors based on antisense and antigene oligonucleotides. Eur J Cancer. 1991; 27:1466-71. Google Scholar15. Chronic myeloid leukaemia: potential for antisense therapy (Editorial). Lancet. 1992; 340:1262-3. Google Scholar16. Ratajczak MZ, Kant JA, Luger SM, Hijiya N, Zhang J, Zon G, et al. In vitro treatment of human leukemia in scid mouse model with c-myb antisense oligodeoxynucleotides. Proc Natl Acad Sci U S A. 1992; 89:11823-7. Google Scholar17. Schwab G, Duroux I, Vhavany C, Goubin G, Helene C, SaisonBehmoaras T. Antisense oligonucleotides stabilized by polyalkylcyanoacrylate nanoparticles specifically inhibit activated Ha-ras mediated proliferation and tumorigenicity (Abstract). International Conference on Antisense Nucleic Acids; 28 February 1993; Germisch-Partenkirchen, Germany. Google Scholar18. Wahlestedt C, Pich EM, Koob GF, Yee F, Heilig M. Modulation of anxiety and neuropeptide Y-Y1 receptors by antisense oligodeoxynucleotides. Science. 1993; 259:528-31. Google Scholar19. Simons M, Edelman ER, DeKeyser JL, Langer R, Rosenberg RD. Antisense c-myb oligonucleotides inhibit intimal arterial smooth muscle cell accumulation in vivo. Nature. 1992; 359:67-70. Google Scholar20. Kirkland MA, O'Brien SG, McDonald C, Davidson RJ, Cross NC, Goldman JM. BCR-ABL antisense purging in chronic myeloid leukaemia (Letter). Lancet. 1993; 342:614. Google Scholar21. Bayever E, Bishop MR, Zon G, Spinolo J, Kessinger A. Human studies using antisense against p53 in AML (Abstract). Cancer Res. 1993; 34:593-4. Google Scholar Author, Article, and Disclosure InformationAffiliations: The Royal North Shore Hospital, Sydney, NSW, Australia 2065. Museum National d'Histoire Naturelle, 75231 Paris, France.Corresponding Author: David D. F. Ma, MBBS, MD, Department of Haematology, The Royal North Shore Hospital, Sydney, NSW, Australia 2065. 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