Antisense oligonucleotide therapeutics for human leukemia

Current Opinion in Hematology

Volumn 5, Issue 1, 1998, Pages 59-71

  Gewirtz, Alan M ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE;

CHRONIC MYELOID LEUKEMIA; CLINICAL MEDICINE; GENE DISRUPTION; GENE THERAPY; HUMAN; LEUKEMIA; PRIORITY JOURNAL; REVIEW;

EID: 0031935087     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/00062752-199801000-00011     Document Type: Review

References (108)

1. Paterson, BM, Roberts BE, Kuff EL: Structural gene identification and mapping by DNA-mRNA hybrid-arrested cell-free translation. Proc Natl Acad Sci USA 1977, 74:4370-4374.
2. Stephenson, ML, Zamecnik PC: Inhibition of Rous sarcoma viral RNA translation by a specific oligodeoxyribonucleotide. Proc Natl Acad Sci USA 1978, 75:285-288.
3. Mizuno, T, Chou MY, lnouye M: A unique mechanism regulating gene expression: translational Inhibition by a complementary RNA transcript (micRNA). Proc Natl Acad Sci USA 1984, 81:1966-1970.
4. Simons, RW, Kleckner N: Biological regulation by antisense RNA prokaryotes. Annu Rev Genet 1988, 22:567-600.
5. Izant, JG, Weintraub H: Constitutive and conditional suppression of exogenous and endogenous genes by anti-sense RNA. Science 1985, 229:345-352.
6. Izant JG, Weintraub H: Inhibition of thymidine Kinase gene expression by anti-sense RNA: a molecular approach to genetic analysis. Cell 1984, 36:1007-1015.
7. Melton, DW: Gene targeting in the mouse. Bioessays 1994, 16:633-638.
8. Helene, C: Rational design of sequence-specific oncogene inhibitors based on antisense and antigene oligonucleotides. Eur J Cancer 1991, 27:1466-1471.
9. Sharma HW, Ferez JR, Higgins-Sochaski K, Hsiao R, Narayanan R: Transcription factor decoy approach to decipher the role of NF-kappa B in oncogenesis. Anticancer Res 1996, 16:61-69.
10. Morishita R, Gibbons GH, Horiuchi M, Ellison KE, Nakama M, Zhang L, Kaneda Y, Oighara T, Dzau VJ: A gene therapy strategy using a transcription factor decoy of the E2F binding site inhibits smooth muscle proliferation in vivo. Proc Natl Acad Sci U S A 1995, 92:5855-5859.
11. Gunther, EJ, Yeasky TM, Gasparro FP, Glazer PM: Mutagenesis by 8-methoxypsoralen and 5-methylangelicin photoadducts in mouse fibroblasts: mutations at cross-linkable sites induced by offoadducts as well as cross-links. Cancer Res 1995, 55:1283-1288.
12. Gunther, EJ, Havre PA, Gasparro FP, Glazer PM: Triplex-mediated, in vitro targeting of psoralen photoadducts within the genome of a transgenic mouse. Photochem Photobiol 1996, 63:207-212.
13. Raha, M, Wang G, Seidman MM, Glazer PM: Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant Proc Natl Acad Sci U S A 1996, 93:2941-2946.
14. Kim, U, Wang Y, Sanford T, Zeng Y, Nishikura K: Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. Proc Natl Acad Sci U S A 1994, 91:11457-11461.
15. Eder, PS, Walder JA: Ribonuclease H from K562 human erythroleukemia cells. Purification, characterization, and substrate specificity. J Biol Chem 1991, 266:6472-6479.
16. Eder, PS, Walder RY, Walder JA: Substrate specificity of human RNase H1 and its role in excision repair of ribose residues misincorporated in DNA. Biochimie 1993, 75:123-126.
17. Stein, CA: Does antisense exist? Nat Med 1995, 1:1119-1121.
18. Nellen, W, Lichtenstein C: What makes an mRNA anti-sense-itive? Trends Biochem Sci 1993, 18:419-423.
19. Ratajczak, MZ, Luger SM, DeRiel K, Abrahm J, Calabretta B, Gewirtz AM: Role of the KIT protooncogene in normal and malignant human hematopoiesis. Proc Natl Acad Sci U S A 1992, 89:1710-1714.
20. Metcalf, D: Blood. Thrombopoletin-at last [comment]. Nature 1994, 369:519-520.
21. Methia, N, Louache F, Vainchenker W, Wendling F: Oligodeoxynucleotides antisense to the proto-oncogene c-mpl specifically inhibit in vitro megakaryocytopoiesis. Blood 1993, 82:1395-1401.
22. Gewirtz, AM, Calabretta B: A c-myb antisense oligodeoxynucleotide inhibits normal human hematopolesis in vitro. Science 1988, 242:1303-1306.
23. Gewirtz, AM, Stein CA, Glazer PM: Facilitating oligonucleotide delivery: helping antisense deliver on its promise. Proc Natl Acad Sci U S A 1996, 93:3161-3163. A short review detailing some of the problems associated with oligonucleotides including issues related to delivery, and targeting.
24. Ratajczak, MZ, Luger SM, Gewirtz AM: The c-kit proto-oncogene in normal and malignant human hematopoiesis. Int J Cell Cloning 1992, 10:205-214.
25. Gewirtz, AM: Potential therapeutic applications of antisense oligodeoxynucleotides in the treatment of chronic myelogenous leukemia. Leuk Lymphoma 1993, 11 (Suppl 1 ):131-137.
26. Gewirtz, AM: Treatment of chronic myelogenous leukemia (CML) with c-myb antisense oligodeoxynucleotides. Bone Marrow Transplant 1994, 14(Suppl 3):S57-S61.
27. Rataczak, MZ, Hijiya N, Catani L, DeRiel K, Luger SM, McGlave P, Gewirtz AM: Acute-and chronic-phase chronic myelogenous leukemia colony-forming units are highly sensitive to the growth inhibitory effects of c-myb antisense oligodeoxynucleotides. Blood 1992, 79:1956-1961.
28. Calabretta, B, Sims RB, Valtieri M, Caracciolo D, Szczylik C, Venturelli D, Ratajczak M, Beran M, Gewirtz AM: Normal and leukemic hematopoietic cells manifest differential sensitivity to inhibitory effects of c-myb antisense oligodeoxynucleotides: an in vitro study relevant to bone marrow purging. Proc Natl Acad Sci U S A 1991, 88:2351-2355.
29. Melo, JV: The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype [editorial; comment] [see comments]. Blood 1996, 88:2375-2384.
30. Szczylik, C, Skorski T, Nicolaides NC, Manzella L, Malaguamera L, Venturelli D, Gerwitz AM, Calabretta B: Selective Inhibition of leukemia cell proliferation by BCR-ABL antisense oligonucleotides. Science 1991, 253:562-565.
31. Skorski, T, Szczylik C, Malaguarnera L, Calabretta B: Gene-targeted specific inhibition of chronic myeloid leukemia cell growth by BCR-ABL antisense oligonucleotldes. Folia Histochem Cytobiol 1991, 29:85-89.
32. Wu, AG, Joshi SS, Chan WC, Iversen PL, Jackson JD, Kessinger A, Pirruccello SJ, Sanger WG, Sharp JG, Verbik DJ, et al.: Effects of BCR-ABL antisense oligonucleotides (AS-ODN) on human chronic myelold leukemic cells: AS-ODN as effective purging agents. Leuk Lymphoma 1995, 20:67-76.
33. de Fabritiis, P, Amadori S, Calabretta B, Mandelli F: Elimination of clonogenic Philadelphia-positive cells using BCR-ABL antisense ollgodeoxynucleotldes. Bone Marrow Transplant 1993, 12:261-265.
34. de Fabritiis, P, Skorski T, De Propris MS, Paggi MG, Nieborowska-Skorska M, Lisa A, Buffolino S, Campbell K, Geiser T, Calabretta B: Effect of bcrabl oligodeoxynucleotides on the clonogenic growth of chronic myelogenous leukaemia cells. Leukemia 1997, 11:811-819. An An in vitro study of the effect of phosphorothioate oligodeoxynucleotides designed to target the brclabl junction on cells derived from 41 patients with Philadelphia-positive CML The study examined optimal oligonucleotide length (16 mer vs 26 mer), and incubation time (1 to 5 days) in a marrow-purging model. The shorter molecule appeared to give more specific results, as did the longer incubation times. Maximal inhibtion of colony formation was ∼60%.
35. Chasty, R, Whetton A, Lucas G: A comparison of the effect of bcr/abl breakpoint specific phosphothlorate oligodeoxynucleotides on colony formation by bcr/abl positiva and negative, CD34 enriched mononuclear cell populations. Leuk Res 1996, 20:391-395.
36. O'Brien, SG, Kirkland MA, Melo JV, Rao MH, Davidson RJ, McDonald C, Goldman JM: Antisense BCR-ABL oligomers cause non-specific inhibition of chronic myeloid leukemia cell lines. Leukemia 1994, 8:2156-2162.
37. 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.
38. Maekawa ,T, Kimura S, Hirakawa K, Murakami A, Zon G, Abe T: Sequence specificity on the growth suppression and Induction of apoptosis of chronic myeloid leukemia cells by BCR-ABL anti-sense oligodeoxynucleoside phosphorothioates. Int J Cancer 1995, 62:63-69.
39. Smetsers, TF, van de Locht LT, Pennings AH, Wessels HM, de Witte TM, Mensink EJ: Phosphorothioate BCR-ABL antisense oligonucleotides induce cell death, but fall to reduce cellular bcr-abl protein levels. Leukemia 1995, 9:118-130.
40. Vaerman, JL, Lammineur C, Moureau P, Lewalle P, Deldime F, Blumenfeld M, Martiat P: BCR-ABL antisense oligodeoxyribonucleotides suppress the growth of leukemic and normal hematopoietic cells by a sequence-specific but nonantisense mechanism. Blood 1995, 86:3891-3896.
41. Mahon, FX, Ripoche J, Pigeonnier V, Jazwiec B, Pigneux A, Moreau JF, Reiffers J: Inhibition of chronic myelogenous leukemia cells harboring a BCR-ABL B3A2 junction by antisense oligonucleotides targeted at the B2A2 junction. Exp Hematol 1995, 23:1606-1611.
42. Leopold LH, Shore SK, Reddy EP: Multi-unit anti-BCR-ABL ribozyme therapy in chronic myelogenous leukemia. Leuk Lymphoma 1996, 22:365-373.
43. Lange, W, Daskalakis M, Finke J, Dolken G: Comparison of different ribozymes for efficient and specific cleavage of BCR/ABL related mRNAs. FEBS Lett 1994, 338:175-178.
44. Pachuk, CJ, Yoon K, Moelling K, Coney LR: Selective cleavage of bcr-abl chimeric RNAs by a ribozyme targeted to non-contiguous sequences. Nucleic Acids Res 1994, 22:301-307.
45. Kronenwett, R, Haas R, Sczakiel G: Kinetic selectivity of complementary • nucleic acids: bcr-abl-directed antisense RNA and ribozymes. J Mol Biol 1996, 259:632-644. An elegant study of factors which determine the efficacy of ribozymes. Ability to rapidly hybridize with the target sequence, as opposed to forming a stable duplex, along with physical accessibility of the targeted sequence within the mRNA are critical elements. Target selectivity was found for a ribozyme that annealed fast via abl sequences and cleaved within the brc portion of brclabl RNA. Kinetic probing and calculations of the local folding potential indicated that the brclabl fusion point sequences were not easily accessible for complementary nucleic acids. The authors conclude, with good supporting data, that more detailed structural investigations of the brc/abl fusion sequence are needed for rational targeting of brc/abl. By implication, all other targets should likely be approached in a similar manner.
46. Rittner, K, Burmester C, Sczakiel G: In vitro selection of fast-hybridizing and effective antisense RNAs directed against the human Immunodeficiency virus type 1. Nucleic Acids Res 1993, 21:1381-1387.
47. Ratajczak, MZ, Kant JA, Luger SM, Hijiya N, Zhang J, Zon G, Gewirtz AM: In vivo treatment of human leukemia in a scid mouse model with c-myb antisense oligodeoxynucleotides. Proc Natl Acad Sci U S A 1992, 88:11823-11827.
48. Skorski, T, Nieborowska-Skorska M, Nicolaides C, Szczylik C, Iversen P, lozzo RV, Zon G, Calabretta B: Suppression of Philadelphia1 leukemia call growth in mice by BCR-ABL antisense oligodeoxynucleotide. Proc Natl Acad Sci U S A 1994, 91:4504-4508.
49. Sawyers, CL, Callahan W, Witte ON: Dominant negative MYC blocks transformation by ABL oncogenes. Cell 1992, 70:901-910.
50. Sawyers, CL: The role of myc in transformation by BCR-ABL Leuk Lymphoma 1993, 11 (Suppl 1):45-46.
51. Skorski, T, Nieborowska-Skorska M, Campbell K, lozzo RV, Zon G, Darzynkiewicz Z, Calabretta B: Leukemia treatment in severe combined immunodeficiency mice by antisense oligodeoxynucleotides targeting cooperating oncogenes. J Exp Med 1995, 182:1645-1653.
52. Skorski, T, Nieborowska-Skorska M, Wlodarski P, Zon G, lozzo RV, Calabretta B: Antisense oligodeoxynucleotide combination therapy of primary chronic myelogenous leukemia blast crisis in SCID mice. Blood 1996, 88:1005-1012.
53. Skorski, T, Nieborowska-Skorska M, Barletta C, Malaguamera L, Szcyzlik C, Chen ST, Lange B, Calabretta B: Highly efficient elimination of Philadelphia leukemic cells by exposure to bcr/abl antisense oligodeoxynucleotides combined with mafosfamide. J Clin Invest 1993, 92:194-202.
54. Skorski, T, Nieborowska-Skorska M, Wlodarski P, Perrotti D, Hoser G, Kawiak J, Majewski M, Christensen L, lozzo RV, Calabretta B: Treatment of Philadelphia leukemia in severe combined immunodeficient mice by combination of cydophosphamide and bcr/abl antisense oligodeoxynucleotides [see comments]. J Natl Cancer Inst 1997, 89:124-133.
55. Bedi, A, Zehnbauer BA, Collector MI, Barber JP, Zicha MS, Sharkis SJ, Jones RJ: BCR-ABL gene rearrangement and expression of primitive hematopoietic progenitors in chronic myeloid leukemia. Blood 1993, 81:2898-2902.
56. Bedi, A, Zehnbauer BA, Barber JP, Sharkis SJ, Jones RJ: Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood 1994, 83:2038-2044.
57. McGahon, A, Bissonnette R, Schmitt M, Cotter KM, Green DR, Cotter TG: BCR-ABL maintains resistance of chronic myelogenous leukemia cells to apoptotic cell death [published erratum appears in Blood 1994 Jun 15; 83(12):3835]. Blood 1994, 83:1179-1187.
58. Kanei-lshii, C, Nomura T, Ogata K, Sarai A, Yasukawa T, Tashiro S, Takahashi T, Tanaka Y, Ishii S: Structure and function of the proteins encoded by the myb gene family. Curr Top Microbiol Immunol 1996, 211:89-98.
59. Nomura, N, Zu YL, Maekawa T, Tabata S, Akiyama T, Ishii S: Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1. J Biol Chem 1993, 268:4259-4266.
60. Biedenkapp, H, Borgmeyer U, Sippel AE, Klempnauer KH: Viral myb oncogene encodes a sequence-specific DNA-binding activity. Nature 1988, 335:835-837.
61. Siu, G, Wurster AL, Lipsick JS, Hedrick SM: Expression of the CD4 gene requires a Myb transcription factor. Mol Cell Biol 1992, 12:1592-1604.
62. Melotti, P, Ku DH, Calabretta B: Regulation of the expression of the hematopoietic stem cell antigen CD34: role of c-myb. J Exp Med 1994, 179:1023-1028.
63. Gewirtz, AM, Anfossi G, Venturelli D, Valpreda S, Sims R, Calabretta B: G1/S transition in normal human T-lymphocytes requires the nuclear protein encoded by c-myb. Science 1989, 245:180-183.
64. Caracciolo, D, Venturelli D, Valtieri M, Peschle C, Gewirtz AM, Calabretta B: Stage-related proliferative activity determines c-myb functional requirements during normal human hematopolesis. J Clin invest 1990, 85:55-61.
65. Mucenski, ML, McLain K, Kier AB, Swerdlow SH, Schreiner CM, Miller TA, Pietryga DW, Scott WJ Jr., Potter SS: A functional c-myb gene is required for normal murine fetal hepatic hematopolesis. Cell 1991, 65:677-689.
66. Anfossi, G, Gewirtz AM, Calabretta B: An oligomer complementary to c-myb-encoded mRNA inhibits proliferation of human myeloid leukemia cell lines. Proc Natl Acad Sci U S A 1989, 86:3379-3383.
67. Melotti, P, Calabretta B: Induction of hematopoietic commitment and erythromyoloid differentiation in embryonal stem cells constitutively expressing c-myb. Blood 1996, 87:2221-2234.
68. Vandenbark, GR, Chen Y, Friday E, Pavlik K, Anthony B, deCastro C, Kaufman RE: Complex regulation of human c-kit transcription by promoter repressors, activators, and specific myb elements. Cell Growth Differ 1996, 7:1383-1392.
69. Ratajczak, M, Perrotti D, Melotti P, Powzaniuk M, Calabretta B, Onodera K, Kregenow D, Machalinski B, Gewirtz A: Myb end Ets Proteins are Candidate Regulators of c-kit Expression in Human Hematopoietic Cells. Blood 1997, in press.
70. Yu, H, Bauer B, Lipke GK, Phillips RL, Van Zant G: Apoptosis and Hematopolesis in Murine Fetal Liver. Blood 1993, 81:373-384.
71. Carson, WE, Haldar S, Baiocchi RA, Croce CM, Caligiuri MA: The c-kit ligand suppresses apoptosis of human natural killer cells through the upregulation of bcl-2. Proc Natl Acad Sci U S A 1994, 91:7553-7557.
72. Bonnefoy-Berard, N, Munshi A, Yron I, Wu S, Collins TL, Deckert M, Shalom-Barak T, Giampa L, Herbert E, Hernandez J, Meller N, Couture C, Altman A: Vav: function and regulation in hematopoletic cell signaling. Stem Cells 1996, 14:250-268.
73. Katzav, S: vav: A molecule for all haemopoiesis? Br J Haematol 1992, 81:141-144.
74. Katzav, S, Martin-Zanca D, Barbacid M: vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoletic cells. Embo J 1989, 8:2283-2290.
75. Katzav, S, Cleveland JL, Heslop HE, Pulido D: Loss of the amino-terminal helix-loop-helix domain of the vav proto-oncogene activates its transforming potential. Mol Cell Biol 1991, 11:1912-1920.
76. Galland, F, Katzav S, Birnbaum D: The products of the mcf-2 and vav proto-oncogenes and of the yeast gene cdc-24 share sequence similarities. Oncogens 1992, 7:585-587.
77. Cen, H, Papageorge AG, Zippel R, Lowry DR, Zhang K: Isolation of multiple mouse cDNAs with coding homology to Saccharomyces cerevisiae CDC25: Identification of a region related to Bcr, Vav, Dbl and CDC24. Embo J 1992, 11:4007-4015.
78. Alai, M, Mui AL, Cutler RL, Bustelo XR, Barbacid M, Krystal G: Steel factor stimulates the tyrosine phosphorylatlon of the proto-oncogene product, p95vav, in human hemopoletic cells. J Biol Chem 1992, 267:18021-18025.
79. Clevenger, CV, Ngo W, Sokol DL, Luger SM, Gewirtz AM: Vav is necessary for prolactin-stimulated proliferation and is translocated into the nucleus of a T-cell line. J Biol Chem 1995, 270:13246-13253.
80. Marengere, LE, Mirtsos C, Kozieradzki I, Veillette A, Mak TW, Penninger JM: Proto-oncoprotein Vav interacts with c-Cbl in activated thymocytes and peripheral T cells. J Immunol 1997, 159:70-76.
81. Coppola, J, Bryant S, Koda T, Conway D, Barbacid M: Mechanism of activation of the vav protooncogene. Cell Growth Differ 1991, 2:95-105.
82. Adams, JM, Houston H, Allen J, Lints T, Harvey R: The hematopoletically expressed vav proto-oncogene shares homology with the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization. Oncogene 1992, 7:611-618.
83. Wulf, GM, Adra CN, Lim B: Inhibition of hematopoletic development from embryonic stem cells by antisense vav RNA. Embo J 1993, 12:5065-5074.
84. Zhang, R, Tsai FY, Orkin SH: Hematopoletic development of vav-/-mouse embryonic stem cells. Proc Natl Acad Sci U S A 1994, 91:12755-12759.
85. Zmuidzinas, A, Fischer KD, Lira SA, Forrester L, Bryant S, Bernstein A, Barbacid M: The vav proto-oncogene is required early in embryogenesis but not for hematopoietic development in vitro. Embo J 1995, 14:1-11.
86. Zhang, R, Alt FW, Davidson L, Orkin SH, Swat W: Defective signalling through the T- and B-cell antigen receptors in lymphold cells lacking the vav proto-oncogene. Nature 1995, 374:470-473.
87. Luger, SM, Ratajczak J, Ratajczak MZ, Kuczynski WI, DiPaola RS, Ngo W, Clevenger CV, Gewirtz AM: A functional analysis of protooncogene Vav's role in adult human hematopoiesls. Blood 1996, 87:1326-1334.
88. Prokocimer, M, Rotter V: Structure and function of p53 in normal cells and their aberrations in cancer cells: projection on the hematologic cell lineages. Blood 1994, 84:2391-2411.
89. Bayever, E, Haines KM, Iversen PL, Ruddon RW, Pirruccello SJ, Mountjoy CP, Ameson MA, Smith LJ: Selective cytotoxlcity to human leukemic myeloblasts produced by oligodeoxyrlbonucleotide phosphorothloates complementary to p53 nucleotide sequences. Leuk Lymphoma 1994, 12:223-231.
90. Bishop, MR, Warkentin PI, Jackson JD, Bayever E, Iversen PL, Whalen VI, Lastovica J, Haines K, Kessinger A: Antisense oligonucleotide OL (1) p53 for in vitro purging of autologous bone marrow in acute myelogenous leukemia. Prog Clin Biol Res 1994, 389:183-187.
91. Reed, JC, Miyashita T, Takayama S, Wang HG, Sato T, Krajewski S, Aime-Sempe C, Bodrug S, Kitada S, Hanada M: BCL-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy. J Cell Biochem 1996, 60:23-32.
92. Gewirtz, AM, Luger S, Sokol D, Gowdin B, Stadtmauer E, Reccio A, Ratajczak MZ: Oligodeoxynucleotide Therapeutics for Human Myelogenous Leukemia: Interim Results. Blood 1996, 88(Supplement 1):270a. Preliminary report of one of the largest series of patients treated with an antisense oligonucleotide. Marrow purging data, as well as results with a systemic infusion, are alluded to.
93. de Fabritis, P, Amadori S, Petti MC, Mancini M, Montefusco E, Picardi A, Geiser T, Campbell K, Calabretta B, Mandelli F: In vitro purging with BCR-ABL antlsense oligodeoxynucleotides does not prevent haematologic reconstitution after autologous bone marrow transplantation. Leukemia 1995, 9:662-664.
94. Bayever, E, Iversen PL, Bishop MR, Sharp JG, Tewary HK, Arneson MA, Pirruccello SJ, Ruddon RW, Kessinger A, Zon G, et al.: Systemic administration of a phosphorothioate oligonucleotide with a sequence complementary to p53 for acute myelogenous leukemia and myelodysplastic syndrome: Initial results of a phase I trial Antisense Res Dev 1993, 3:383-390.
95. Bishop, MR, Iversen PL, Bayever E, Sharp JG, Greiner TC, Copple BL Ruddon R, Zon G, Spinolo J, Ameson M, Armitage JO, Kessinger A: Phase I trial of an antisense oligonucleotide OL(1)p53 in hematologic malignancies. J Clin Oncol 1996, 14:1320-1326. One of a handful of clinical studies using an antisense olgionucleotide, in this case targeted to the p53 gene. The rationale for this target was, and remains controversial. Little in the way of therapeutic efficiacy was demonstrated and there was no correlation with effects on the targeted mRNA. The material was well tolerated for the most part, and the accompanying pharmacokinetic data are of interest.
96. Cotter, FE, Johnson P, Hall P, Pocock C, al Mahdi N, Cowell JK, Morgan G: Antlsense oilgonucteotides suppress B-cell lymphoma growth in a SCID-hu mouse model. Oncogens 1994, 9:3049-3055.
97. Webb, A, Cunningham D, Cotter F, Clarke PA, di Stefano F, Ross P, Corbo M, Dziewanowska Z: BCL-2 antisense therapy in patiants with non-Hodgkin lymphoma. Lancet 1997, 349:1137-1141. An interesting clinical study examining the effect of a bcl-2-targeted oligionucleotide in patients with refractory non-Hodgkin lymphoma. Material (18nt phoaphorothioate) was delivered to nine patients by dairy subcutaneous infusion for 2 weeks. Efficacy was assessed clinically and correlated with effects of BCL-2 protein expression. Therapy was associated with an improvement in symptoms, objective biochemical and radiological evidence of tumour response, and downregulation of the BCL-2 protein in some patients.
98. Loke, SL, Stein CA, Zhang XH, Mori K, Nakaniski M, Subasinghe C, Cohen JS, Neckers LM: Characterization of oligonucleotide transport into living cells. Proc Natl Acad Sci U S A 1989, 86:3474-3478.
99. Beltinger, C, Saragovi HU, Smith RM, LeSauteur L, Shah N, DeDionisio L, Christensen L, Raible A, Jarett L, Gewirtz AM: Binding, uptake, and Intracellular trafficking of phosphorothioate-modified oligodeoxynucleotides. J Clin Invest 1995, 95:1814-1823.
100. Stein, CA, Mori K, Loke SL, Subasinghe C, Shinozuka K, Cohen JS, Neckers LM: Phosphorothioate and normal oligodeoxyribonucleotides with 5′-linked acridine: characterization and preliminary kinetics of cellular uptake. Gene 1988, 72:333-341.
101. Geselowitz, DA, Neckers LM: Analysis of oligonucleotide binding, Internalization, and intracellular trafficking utilizing a novel radiolabeled crosslinker. Antisense Res Dev 1992, 2:17-25.
102. Spiller, DG, Tidd DM: Nuclear delivery of antisense oligodeoxynucleotides through reversible permeabillzation of human leukemia cells with streptolysin O. Antisense Res Dev 1995, 5:13-21.
103. Lewis, JG, Lin KY, Kothavale A, Flanagan WM, Matteucci MD, DePrince RB, Mook RA, Hendren RW, Wagner RW: A serum-resistant cytofectin for cellular delivery of antisense oligodeoxynucleotides and plasmid DNA. Proc Natl Acad Sci, U S A 1996, 93:3176-3181. Describes a potentially useful lipid cytofectin for delivering oligonucleotides to cells.
104. Bergan, R, Hakim F, Schwarte GN, Kyle E, Cepada R, Szabo JM, Fowler D, Grass R, Neckers L: Electroporation of synthetic oligodeoxynucleotides: a novel technique for ex vivo bone marrow purging. Blood 1996, 88:731-741. Suggests electorporation as a method for efficiently delivering oligonucleotides to hematopoietic cells.
105. Baskerville, S, Ellington AD: RNA structure. Describing the elephant Curr Biol 1995, 5:120-123.
106. Milner, N, Mir KU, Southern EM: Selecting effective antisense reagents on combinatorial oligonucleotide arrays [see comments]. Nat Biotechnol 1997, 15:537-541. An example of "chip technology" rapid screening of oligonucleotides capable of hybridizing with a specific mRNA target. An array of 1,938 oligodeoxynucleotides ranging in length from monomers to 17-mers was fabricated on the surface of a glass plate. The potential ability of any of the oligonucleotides for heteroduplex formation with rabbit beta-globin mRNA was measured. Antisense activity, measured in a RNase H assay and by in vitro translation, correlated well with yield of heteroduplex on the array. The authors found no obvious features in the mRNA sequence or the predicted secondary structure that could explain the variation in heteroduplex yield. The likely explanation is that folding in vivo is not really predicted very well using present technology. The efficacy of the oligodeoxynucleotide selected in an in vivo assay was not explored, a clearly important ommission in evaluating the overall utility of this approach.
107. 1r RW: The state of the art in antisense research. Nat Med 1995, 1:1116-1118.
108. Stein, CA, Krieg AM: Problems in Interpretation of data derived from in vitro and in vivo use of antisense oligodeoxynucleotides [editorial]. Antisense Res Dev 1994, 4:67-69.