antisense oligonucleotides

Summary

Summary: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.

Top Publications

  1. ncbi Local dystrophin restoration with antisense oligonucleotide PRO051
    Judith C van Deutekom
    Department of Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
    N Engl J Med 357:2677-86. 2007
  2. ncbi RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform
    C Frank Bennett
    Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    Annu Rev Pharmacol Toxicol 50:259-93. 2010
  3. pmc Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis
    Angie M Cheng
    Ambion, Inc 2130 Woodward Street, Austin, TX 78744 1832, USA
    Nucleic Acids Res 33:1290-7. 2005
  4. ncbi Antisense oligonucleotides: basic concepts and mechanisms
    Nathalie Dias
    Columbia University, New York, New York 10032, USA
    Mol Cancer Ther 1:347-55. 2002
  5. ncbi LNA: a versatile tool for therapeutics and genomics
    Michael Petersen
    Nucleic Acid Center, Dept of Chemistry, University of Southern Denmark, DK 5230 Odense M, Denmark
    Trends Biotechnol 21:74-81. 2003
  6. ncbi Controlling morpholino experiments: don't stop making antisense
    Judith S Eisen
    Institute of Neuroscience, 1254 University of Oregon, Eugene, OR 97403 1254, USA
    Development 135:1735-43. 2008
  7. ncbi Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92
    H Matsubara
    Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Showa Ku, Nagoya, Japan
    Oncogene 26:6099-105. 2007
  8. pmc Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development
    Wigard P Kloosterman
    Hubrecht Laboratory KNAW, Utrecht, The Netherlands
    PLoS Biol 5:e203. 2007
  9. pmc Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents
    C A Stein
    Albert Einstein Montefiore Cancer Center, Montefiore Medical Center, Bronx, NY 10467, USA
    Nucleic Acids Res 38:e3. 2010
  10. ncbi Identification of mcl-1 as a BCR/ABL-dependent target in chronic myeloid leukemia (CML): evidence for cooperative antileukemic effects of imatinib and mcl-1 antisense oligonucleotides
    Karl J Aichberger
    Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, AKH Wien, Waehringer Guertel 18 20, A 1097 Vienna, Austria
    Blood 105:3303-11. 2005

Detail Information

Publications385 found, 100 shown here

  1. ncbi Local dystrophin restoration with antisense oligonucleotide PRO051
    Judith C van Deutekom
    Department of Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
    N Engl J Med 357:2677-86. 2007
    ..We explored the safety, adverse-event profile, and local dystrophin-restoring effect of a single, intramuscular dose of an antisense oligonucleotide, PRO051, in patients with this disease...
  2. ncbi RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform
    C Frank Bennett
    Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    Annu Rev Pharmacol Toxicol 50:259-93. 2010
    ..b>Antisense oligonucleotides are perhaps the most direct therapeutic strategy to approach RNA...
  3. pmc Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis
    Angie M Cheng
    Ambion, Inc 2130 Woodward Street, Austin, TX 78744 1832, USA
    Nucleic Acids Res 33:1290-7. 2005
    ..From these screens, we conclude that miRNA-mediated regulation has a complexity of cellular outcomes and that miRNAs can be mediators of regulation of cell growth and apoptosis pathways...
  4. ncbi Antisense oligonucleotides: basic concepts and mechanisms
    Nathalie Dias
    Columbia University, New York, New York 10032, USA
    Mol Cancer Ther 1:347-55. 2002
  5. ncbi LNA: a versatile tool for therapeutics and genomics
    Michael Petersen
    Nucleic Acid Center, Dept of Chemistry, University of Southern Denmark, DK 5230 Odense M, Denmark
    Trends Biotechnol 21:74-81. 2003
    ..Furthermore, convincing examples of the application of LNA to nucleic acid diagnostics have been reported, including high capturing efficiencies and unambiguous scoring of single-nucleotide polymorphisms...
  6. ncbi Controlling morpholino experiments: don't stop making antisense
    Judith S Eisen
    Institute of Neuroscience, 1254 University of Oregon, Eugene, OR 97403 1254, USA
    Development 135:1735-43. 2008
    ..A widely adopted approach is to use antisense technologies, and especially morpholino antisense oligonucleotides. In this article, we review the use of such reagents and present examples of how they have provided ..
  7. ncbi Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92
    H Matsubara
    Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Showa Ku, Nagoya, Japan
    Oncogene 26:6099-105. 2007
    ..In the present study, we show that inhibition of miR-17-5p and miR-20a with antisense oligonucleotides (ONs) can induce apoptosis selectively in lung cancer cells overexpressing miR-17-92, suggesting the ..
  8. pmc Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development
    Wigard P Kloosterman
    Hubrecht Laboratory KNAW, Utrecht, The Netherlands
    PLoS Biol 5:e203. 2007
    ..The miRNA knockdown strategy presented here will be widely used to unravel miRNA function in zebrafish...
  9. pmc Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents
    C A Stein
    Albert Einstein Montefiore Cancer Center, Montefiore Medical Center, Bronx, NY 10467, USA
    Nucleic Acids Res 38:e3. 2010
    ..The establishment of this link is of particular significance to those in the academic research and drug discovery and development communities...
  10. ncbi Identification of mcl-1 as a BCR/ABL-dependent target in chronic myeloid leukemia (CML): evidence for cooperative antileukemic effects of imatinib and mcl-1 antisense oligonucleotides
    Karl J Aichberger
    Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, AKH Wien, Waehringer Guertel 18 20, A 1097 Vienna, Austria
    Blood 105:3303-11. 2005
    ..To investigate the role of MCL-1 as a survival-related target in CML cells, mcl-1 siRNA and mcl-1 antisense oligonucleotides (ASOs) were applied...
  11. ncbi Therapeutic modulation of DMD splicing by blocking exonic splicing enhancer sites with antisense oligonucleotides
    A Aartsma-Rus
    Department of Human Genetics, DMD Genetic Therapy Group, Leiden University Medical Center, 2333 AL Leiden, The Netherlands
    Ann N Y Acad Sci 1082:74-6. 2006
    b>Antisense oligonucleotides (AONs) can be used to correct the disrupted reading frame of Duchenne muscular dystophy patients (DMD)...
  12. pmc Therapeutic potential of antisense oligonucleotides as modulators of alternative splicing
    Peter Sazani
    University of North Carolina, Lineberger Comprehensive Cancer Center, CB 7295, Chapel Hill, North Carolina 27599 7295, USA
    J Clin Invest 112:481-6. 2003
    ..This Perspective describes a promising approach to RNA repair based on the use of antisense oligonucleotides to modulate alternative splicing and engender the production of therapeutic gene products.
  13. ncbi A phase I pharmacokinetic and pharmacodynamic study of OGX-011, a 2'-methoxyethyl antisense oligonucleotide to clusterin, in patients with localized prostate cancer
    Kim N Chi
    Vancouver Cancer Centre, BC Cancer Agency, Vancouver, British Columbia, V5Z 4E6, Canada
    J Natl Cancer Inst 97:1287-96. 2005
    ..The primary objective of this clinical study was to determine a biologically effective dose of OGX-011 that would inhibit clusterin expression in human cancer...
  14. ncbi In vivo comparison of 2'-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping
    Hans A Heemskerk
    DMD Genetic Therapy Group, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    J Gene Med 11:257-66. 2009
    Antisense-mediated exon skipping is a putative treatment for Duchenne muscular dystrophy (DMD). Using antisense oligonucleotides (AONs), the disrupted DMD reading frame is restored, allowing generation of partially functional dystrophin ..
  15. pmc Enhancement of SMN2 exon 7 inclusion by antisense oligonucleotides targeting the exon
    Yimin Hua
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America
    PLoS Biol 5:e73. 2007
    ..b>Antisense oligonucleotides (ASOs) that target an exon or its flanking splice sites usually promote exon skipping...
  16. ncbi Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function
    HaiFang Yin
    Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK
    Hum Mol Genet 17:3909-18. 2008
    b>Antisense oligonucleotides (AOs) have the potential to induce functional dystrophin protein expression via exon skipping by restoring in-frame transcripts in the majority of patients suffering from Duchenne muscular dystrophy (DMD)...
  17. ncbi Morpholino antisense oligomers: the case for an RNase H-independent structural type
    J Summerton
    Gene Tools, Corvallis, OR 97339, USA
    Biochim Biophys Acta 1489:141-58. 1999
    ....
  18. ncbi Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance
    T Robson
    Radiation Science Group, School of Biomedical Sciences, University of Ulster, Newtownabbey, N Ireland, UK
    Int J Radiat Biol 76:617-23. 2000
    To determine whether repression of a recently isolated, X-ray-responsive gene, DIR1, using antisense oligonucleotides could affect clonogenic cell survival and repair of DNA strand breaks and have a possible role in the mechanism ..
  19. ncbi Antitumor activity of antisense clusterin oligonucleotides is improved in vitro and in vivo by incorporation of 2'-O-(2-methoxy)ethyl chemistry
    T Zellweger
    The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada
    J Pharmacol Exp Ther 298:934-40. 2001
    Phosphorothioate (P=S) antisense oligonucleotides (ASO) targeting the cell survival gene clusterin synergistically enhance castration- and chemotherapy-induced apoptosis in prostate cancer xenografts...
  20. pmc In vivo tumor growth inhibition and biodistribution studies of locked nucleic acid (LNA) antisense oligonucleotides
    Kees Fluiter
    Department of Neurogenetics, Academical Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    Nucleic Acids Res 31:953-62. 2003
    ..In this study we tested the biological fate and the efficacy in tumor growth inhibition of antisense oligonucleotides directed against the gene of the large subunit of RNA polymerase II (POLR2A) that are completely ..
  21. ncbi Correction of alternative splicing of tau in frontotemporal dementia and parkinsonism linked to chromosome 17
    B Kalbfuss
    National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:42986-93. 2001
    ..that alternative splicing defects of tau as found in FTDP-17 patients can be corrected by application of antisense oligonucleotides. These findings provide a tool to study specific tau isoforms in vivo and might lead to a novel ..
  22. ncbi Oral delivery of siRNA and antisense oligonucleotides
    Saghir Akhtar
    Department of Pharmacology and Toxicology, Faculty of Medicine, Health Sciences Center, Kuwait University, Safat, Kuwait
    J Drug Target 17:491-5. 2009
    Inhibition of gene expression with antisense oligonucleotides or RNA interference (RNAi) mediated gene silencing by small interfering RNA (siRNA) has tremendous potential to silence the expression of disease-causing genes in the clinic...
  23. pmc Design of LNA probes that improve mismatch discrimination
    Yong You
    Integrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA
    Nucleic Acids Res 34:e60. 2006
    ..New guidelines are suggested for design of LNA probes, which significantly improve mismatch discrimination in comparison with unmodified DNA probes...
  24. pmc Kinetic characteristics of Escherichia coli RNase H1: cleavage of various antisense oligonucleotide-RNA duplexes
    S T Crooke
    Isis Pharmaceuticals, Inc, Carlsbad, CA 92008, USA
    Biochem J 312:599-608. 1995
    ..of variations in substrates on the kinetic properties of Escherichia coli RNase H were studied using antisense oligonucleotides of various types hybridized to complementary oligoribonucleotides...
  25. pmc The influence of locked nucleic acid residues on the thermodynamic properties of 2'-O-methyl RNA/RNA heteroduplexes
    Elzbieta Kierzek
    Department of Chemistry, University of Rochester RC Box 270216, Rochester, NY 14627 0216, USA
    Nucleic Acids Res 33:5082-93. 2005
    ..Internal mismatches with LNA nucleotides significantly destabilize duplexes with RNA...
  26. ncbi Therapeutic potentialities of EWS-Fli-1 mRNA-targeted vectorized antisense oligonucleotides
    A Maksimenko
    BioAlliance Pharma, 59, Boulevard du Général Martial Valin, 75015 Paris
    Ann N Y Acad Sci 1002:72-7. 2003
    We have used structured antisense oligonucleotides (AON), which are protected against extra and intracellular degradation by their internal structure...
  27. pmc Nanotechnologies and controlled release systems for the delivery of antisense oligonucleotides and small interfering RNA
    Elias Fattal
    Univ Paris Sud 11, UMR 8612, Chatenay Malabry, F 92290, France
    Br J Pharmacol 157:179-94. 2009
    b>Antisense oligonucleotides and small interfering RNA have enormous potential for the treatment of a number of diseases, including cancer...
  28. ncbi State of the art and perspectives for the delivery of antisense oligonucleotides and siRNA by polymeric nanocarriers
    Elias Fattal
    Univ Paris Sud 11, UMR 8612, Châtenay Malabry F 92290, France
    Int J Pharm 364:237-48. 2008
    Knocking down gene expression using either antisense oligonucleotides (AS-ODNs) or small interfering RNA (siRNAs) has raised a lot of interest in designing new pathways for therapeutics...
  29. pmc Mechanisms and strategies for effective delivery of antisense and siRNA oligonucleotides
    Rudy Juliano
    Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA
    Nucleic Acids Res 36:4158-71. 2008
    ..Thus, choice of an optimal delivery modality will likely depend on the therapeutic context...
  30. ncbi In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes
    Wigard P Kloosterman
    Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Nat Methods 3:27-9. 2006
    ..Here we performed a detailed analysis of conditions for in situ detection of miRNAs in the zebrafish embryo using locked nucleic acid (LNA)-modified DNA probes and report expression patterns for 15 miRNAs in the mouse embryo...
  31. ncbi Enhanced radiation sensitivity in prostate cancer by inhibition of the cell survival protein clusterin
    Tobias Zellweger
    The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia V6H 3Z6, Canada
    Clin Cancer Res 8:3276-84. 2002
    ..Experimental Design: Radiation sensitivities were compared in parental and clusterin-overexpressing LNCaP cells and in PC-3 cells and tumors treated with antisense or mismatch clusterin oligonucleotides...
  32. ncbi Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugs
    Hongjiang Wu
    Department of Core Technology, Isis Pharmaceuticals, Inc, Carlsbad, California 92008, USA
    J Biol Chem 279:17181-9. 2004
    ..Further, we show that there are several additional previously undescribed RNases H in human cells that may participate in the effects of DNA-like antisense oligonucleotides.
  33. ncbi Efficient and persistent splice switching by systemically delivered LNA oligonucleotides in mice
    Jennifer Roberts
    Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, CB 7295, Chapel Hill, NC 27599 7295, USA
    Mol Ther 14:471-5. 2006
    ....
  34. ncbi The protooncogene c-myc is an essential regulator of neural crest formation in xenopus
    Amy Bellmeyer
    Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208, USA
    Dev Cell 4:827-39. 2003
    ..These effects are not dependent upon changes in cell proliferation or cell death. Instead, our findings reveal an important and unexpected role for c-Myc in the specification of cell fates in the early ectoderm...
  35. ncbi Critical role of Lyn kinase in inhibition of neutrophil apoptosis by granulocyte-macrophage colony-stimulating factor
    S Wei
    Immunology Program, H Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa 33612, USA
    J Immunol 157:5155-62. 1996
    ..Therefore, the physical coupling of Lyn to GM-CSF receptor and its early activation are required for inhibition or delay of apoptosis in PMN...
  36. ncbi The yolk syncytial layer regulates myocardial migration by influencing extracellular matrix assembly in zebrafish
    Takuya Sakaguchi
    Department of Biochemistry and Biophysics and Programs in Developmental Biology, Genetics and Human Genetics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 2711, USA
    Development 133:4063-72. 2006
    ..Based on these data, we propose that the extra-embryonic YSL regulates myocardial migration, at least in part by influencing fibronectin expression and subsequent assembly of the extracellular matrix in embryonic tissues...
  37. ncbi Specific inhibition of cyclooxygenase-2 results in inhibition of proliferation of oral cancer cell lines via suppression of prostaglandin E2 production
    K Sumitani
    Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan
    J Oral Pathol Med 30:41-7. 2001
    ..These results suggest that specific inhibition of COX-2 inhibits proliferation of cancer cells expressing COX-2 mRNA via suppression of PGE2 production...
  38. ncbi Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 30:293-9. 2009
    ..Further research is needed to determine the functionality of different in-frame dystrophins and a number of hurdles has to be overcome before this approach can be applied clinically...
  39. ncbi Targeted suppression of an amyloidogenic transthyretin with antisense oligonucleotides
    Merrill D Benson
    Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 128, Indianapolis, Indiana 46202 5126, USA
    Muscle Nerve 33:609-18. 2006
    ..As a first step toward medical treatment of this disease, we have employed antisense oligonucleotides (ASOs) to inhibit hepatic expression of TTR...
  40. ncbi Local injection of antisense oligonucleotides targeted to the glial glutamate transporter GLAST decreases the metabolic response to somatosensory activation
    N Cholet
    Laboratory of Cerebrovascular Research, CNRS UPR646, University of Paris 7, Paris, France
    J Cereb Blood Flow Metab 21:404-12. 2001
    ..Results indicate that astrocytes should also be considered as possible sources of altered brain metabolism that could explain the distinct imaging signals observed in some pathologic situations...
  41. pmc Brothers in arms: DNA enzymes, short interfering RNA, and the emerging wave of small-molecule nucleic acid-based gene-silencing strategies
    Ravinay Bhindi
    Centre for Vascular Research, The University of New South Wales, Sydney, NSW 2052, Australia
    Am J Pathol 171:1079-88. 2007
    ..therapeutics encompasses a range of agents that include DNA enzymes, short interfering RNA, antisense oligonucleotides, decoys, ribozymes, and aptamers...
  42. ncbi Progress towards in vivo use of siRNAs
    Mark A Behlke
    Integrated DNA Technologies, Inc, Coralville, IA 52241, USA
    Mol Ther 13:644-70. 2006
    ..This review will first discuss aspects of RNAi biochemistry and biology that impact in vivo use, especially as relates to experimental design, and will then provide an overview of published work with a focus on methodology...
  43. ncbi Novel antisense oligonucleotides targeting TGF-beta inhibit in vivo scarring and improve surgical outcome
    M F Cordeiro
    Department of Pathology and Glaucoma, London, UK
    Gene Ther 10:59-71. 2003
    ..05) and improved surgical outcome. Our findings suggest that TGF-beta antisense oligonucleotides have potential as a new therapy for reducing post-surgical scarring...
  44. pmc Morpholino antisense oligonucleotides: tools for investigating vertebrate development
    D R Corey
    Departments of Pharmacology and Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    Genome Biol 2:REVIEWS1015. 2001
    b>Antisense oligonucleotides provide a promising approach to investigating gene function in vivo, but their ability to offer unambiguous insights into phenotypes has been debated...
  45. ncbi Molecular basis for target RNA recognition and cleavage by human RISC
    Stefan Ludwig Ameres
    Max F Perutz Laboratories, University of Vienna, Vienna, Austria
    Cell 130:101-12. 2007
    ..We therefore provide mechanistic insights by revealing features of RISC and target RNAs that are crucial to achieve efficiency and specificity in RNA interference...
  46. ncbi Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice
    Mark J Graham
    Cardiovascular Group, Department of Antisense Drug Discovery, Isis Pharmaceuticals, Inc, Carlsbad, CA 92008, USA
    J Lipid Res 48:763-7. 2007
    ..Antisense inhibition of PCSK9 is an attractive and novel therapeutic approach for treating hypercholesterolemia in human...
  47. ncbi Antisense therapy for cancer
    Martin E Gleave
    The Prostate Centre at Vancouver General Hospital, and Division of Urology, University of British Columbia D9, Canada, V5Z 355
    Nat Rev Cancer 5:468-79. 2005
    ..b>Antisense oligonucleotides offer one approach to target genes involved in cancer progression, especially those that are not ..
  48. ncbi Therapeutic potential for microRNAs
    Christine C Esau
    Isis Pharmaceuticals, 1896 Rutherford Road, Carlsbad, California 92008, USA
    Adv Drug Deliv Rev 59:101-14. 2007
    ..The next few years should see significant progress in our understanding of miRNA biology and the advancement of the technology for therapeutic modulation of miRNA activity...
  49. ncbi Antisense oligonucleotide-based therapeutics for cancer
    Nicholas M Dean
    Isis Pharmaceuticals, 2282 Faraday Ave, Carlsbad, CA 92008, USA
    Oncogene 22:9087-96. 2003
    ..We now have a far better appreciation of the attributes and limitations of the technology. Antisense oligonucleotides have been used to selectively inhibit thousands of genes in mammalian cells, hundreds, if not thousands, ..
  50. ncbi In vitro evaluation of novel antisense oligonucleotides is predictive of in vivo exon skipping activity for Duchenne muscular dystrophy
    Qingsong Wang
    State Key Laboratory of AgroBiotech, The Life Science Research Centre, China Agricultural University, Beijing, China
    J Gene Med 12:354-64. 2010
    Targeted splice modulation of pre-mRNA transcripts by antisense oligonucleotides (AOs) can correct the function of aberrant disease-related genes...
  51. ncbi Use of antisense oligonucleotides targeting the cytoprotective gene, clusterin, to enhance androgen- and chemo-sensitivity in prostate cancer
    Martin Gleave
    Division of Urology, University of British Columbia, D 9, 2733 Heather Street, Vancouver, British Columbia, V5Z 3J5, Canada
    World J Urol 23:38-46. 2005
    ..Here, we review clusterin's functional role in apoptosis and the use of antisense oligonucleotides (ASOs) against clusterin to enhance apoptosis in prostate cancer models...
  52. ncbi Comparative analysis of antisense oligonucleotide analogs for targeted DMD exon 46 skipping in muscle cells
    A Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg, AL Leiden, The Netherlands
    Gene Ther 11:1391-8. 2004
    As small molecule drugs for Duchenne muscular dystrophy (DMD), antisense oligonucleotides (AONs) have been shown to restore the disrupted reading frame of DMD transcripts by inducing specific exon skipping...
  53. ncbi Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells
    Jennifer Machen
    Diabetes Institute, Department of Pediatrics, University of Pittsburgh School of Medicine, PA 15213, USA
    J Immunol 173:4331-41. 2004
    ..cell surface molecules were specifically down-regulated by treating NOD DCs ex vivo with a mixture of antisense oligonucleotides targeting the CD40, CD80, and CD86 primary transcripts...
  54. ncbi Zebrafish Dpr2 inhibits mesoderm induction by promoting degradation of nodal receptors
    Lixia Zhang
    Laboratory of Developmental Biology, Ministry of Education MOE, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China
    Science 306:114-7. 2004
    ..Dpr2 is localized in late endosomes, binds to the TGFbeta receptors ALK5 and ALK4, and accelerates lysosomal degradation of these receptors...
  55. ncbi Knock-down of Bcl-2 by antisense oligodeoxynucleotides induces radiosensitization and inhibition of angiogenesis in human PC-3 prostate tumor xenografts
    Satoshi Anai
    Department of Urology, College of Medicine, University of Florida, Suite N2 3, P O Box 100247, Gainesville, FL, USA
    Mol Cancer Ther 6:101-11. 2007
    ..Together, these findings warrant further study of this novel combination of Bcl-2 reduction and radiation therapy, as well as Bcl-2 reduction and angiogenic therapy...
  56. pmc Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals
    Eric E Swayze
    Isis Pharmaceuticals, Inc, 1896 Rutherford Road, Carlsbad, CA 92008, USA
    Nucleic Acids Res 35:687-700. 2007
    A series of antisense oligonucleotides (ASOs) containing either 2'-O-methoxyethylribose (MOE) or locked nucleic acid (LNA) modifications were designed to investigate whether LNA antisense oligonucleotides (ASOs) have the potential to ..
  57. ncbi Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth
    Y Wang
    Department of Pathology, University of Pittsburgh, Pennsylvania 15213, USA
    Nat Med 3:887-93. 1997
    ..Thus, inhibition of bFGF/FGFR-1-mediated signaling may open a new avenue for the treatment of advanced-stage melanomas...
  58. ncbi Bactericidal antisense effects of peptide-PNA conjugates
    L Good
    Center for Genomics Research, Karolinska Institute, Berzelius väg 37, 171 77, Stockholm, Sweden
    Nat Biotechnol 19:360-4. 2001
    ..These results indicate that peptides can be used to carry antisense PNA agents into bacteria. Such peptide-PNA conjugates open exciting possibilities for anti-infective drug development and provide new tools for microbial genetics...
  59. pmc The biological effect of an antisense oligonucleotide depends on its route of endocytosis and trafficking
    Md Rowshon Alam
    Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Oligonucleotides 20:103-9. 2010
    ..We determined that the RGD-SSO and the unconjugated SSO were internalized by distinct endocytotic pathways, suggesting that the route of internalization affects the magnitude of the biological response...
  60. pmc Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate
    S M Elbashir
    Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D 37077 Gottingen, Germany
    EMBO J 20:6877-88. 2001
    ..The position of the cleavage site in the target RNA is defined by the 5' end of the guide siRNA rather than its 3' end. These results provide a rational basis for the design of siRNAs in future gene targeting experiments...
  61. ncbi Conjugates of antisense oligonucleotides with the Tat and antennapedia cell-penetrating peptides: effects on cellular uptake, binding to target sequences, and biologic actions
    Anna Astriab-Fisher
    Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599, USA
    Pharm Res 19:744-54. 2002
    ..of effective intracellular delivery remains an important issue for pharmacologic applications of antisense oligonucleotides. Here, we describe the synthesis, binding properties, and biologic properties of peptide-oligonucleotide ..
  62. ncbi Neuroblastoma targeting by c-myb-selective antisense oligonucleotides entrapped in anti-GD2 immunoliposome: immune cell-mediated anti-tumor activities
    Chiara Brignole
    Laboratory of Oncology, Giannina Gaslini Children s Hospital, Largo Gerolamo Gaslini, 5, 16148 Genova, Italy
    Cancer Lett 228:181-6. 2005
    ..Immunoliposomes can be used as vectors to deliver antisense oligonucleotides to cancer cells with the aim to modulate oncogene expression...
  63. ncbi Liver-specific inhibition of acyl-coenzyme a:cholesterol acyltransferase 2 with antisense oligonucleotides limits atherosclerosis development in apolipoprotein B100-only low-density lipoprotein receptor-/- mice
    Thomas A Bell
    Department of Pathology, Section on Lipid Sciences, Wake Forest University Health Sciences, Medical Center Blvd, Winston Salem, NC 27157, USA
    Arterioscler Thromb Vasc Biol 26:1814-20. 2006
    ..The purpose of this study was to determine the effects of liver-specific inhibition of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) on the development of hypercholesterolemia and atherosclerosis in mice...
  64. ncbi Techniques and probes for the study of Xenopus tropicalis development
    Mustafa K Khokha
    Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA
    Dev Dyn 225:499-510. 2002
    ..We show that MOs function in X. tropicalis. Finally, X. tropicalis offers the possibility for forward genetics and genomic analysis...
  65. ncbi Functional genomics tools for the analysis of zebrafish pigment
    Michael A Pickart
    Department of Oral Sciences and Minnesota Craniofacial Research Training Program MinnCResT, University of Minnesota, Minneapolis, MN, USA
    Pigment Cell Res 17:461-70. 2004
    ....
  66. pmc Antisense oligonucleotides from the stage-specific myeloid zinc finger gene MZF-1 inhibit granulopoiesis in vitro
    L Bavisotto
    Department of Medicine, University of Washington, Seattle 98195
    J Exp Med 174:1097-101. 1991
    ..Antisense but not sense oligonucleotides from MZF-1 significantly inhibited granulocyte colony-stimulating factor-driven granulocyte colony formation in vitro...
  67. pmc Antisense oligonucleotides targeted to the domain IIId of the hepatitis C virus IRES compete with 40S ribosomal subunit binding and prevent in vitro translation
    Béatrice Tallet-Lopez
    INSERM U386, Universite Victor Segalen, 146 rue Leo Saignat, 33076 Bordeaux, France
    Nucleic Acids Res 31:734-42. 2003
    ....
  68. ncbi Exploring cellular activity of locked nucleic acid-modified triplex-forming oligonucleotides and defining its molecular basis
    Erika Brunet
    Laboratoire de Biophysique, Muséum National d Histoire Naturelle USM 503, CNRS UMR 5153, INSERM U 565, Paris, France
    J Biol Chem 280:20076-85. 2005
    ..We provide evidence of their biological activity by a triplex-based mechanism, in vitro and in a cellular context, under conditions in which the parent phosphodiester oligonucleotide did not exhibit any inhibitory effect...
  69. pmc Efficient cytosolic delivery of molecular beacon conjugates and flow cytometric analysis of target RNA
    Antony K Chen
    Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    Nucleic Acids Res 36:e69. 2008
    ..Overall, the present study introduces an improved methodology for the high-throughput detection of RNA at the single cell level...
  70. ncbi The beta-catenin/VegT-regulated early zygotic gene Xnr5 is a direct target of SOX3 regulation
    Chi Zhang
    Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309 0347, USA
    Development 130:5609-24. 2003
    ..These observations indicate that maternal XSOX3 acts in a novel manner to restrict Xnr5 expression to the vegetal hemisphere...
  71. ncbi Methods for introducing morpholinos into the chicken embryo
    Robert Kos
    Section of Molecular and Cellular Biology, University of California Davis, Davis, California 95616, USA
    Dev Dyn 226:470-7. 2003
    ....
  72. ncbi Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides
    S D Wilton
    Department of Pathology, Australian Neuromuscular Research Institute, University of Western Australia, QE II Medical Centre, Nedlands, Australia
    Neuromuscul Disord 9:330-8. 1999
    ..b>Antisense oligonucleotides have been shown to block aberrant splicing in the human beta-globin gene...
  73. pmc Cell-penetrating peptides as transporters for morpholino oligomers: effects of amino acid composition on intracellular delivery and cytotoxicity
    Rebecca P Wu
    AVI BioPharma, Inc, Corvallis, OR 97333, USA
    Nucleic Acids Res 35:5182-91. 2007
    ..Toxicity of X/B-containing conjugates was affected by the number of Xs, treatment time and concentration. More active, stable and less toxic CPPs can be designed by optimizing the position and number of R, D-R, X and B residues...
  74. ncbi Short antisense oligonucleotides with novel 2'-4' conformationaly restricted nucleoside analogues show improved potency without increased toxicity in animals
    Punit P Seth
    Isis Pharmaceuticals, 1891 Rutherford Road, Carlsbad, California 92008, USA
    J Med Chem 52:10-3. 2009
    The potency of second generation antisense oligonucleotides (ASOs) in animals was increased 3- to 5 -fold (ED(50) approximately 2-5 mg/kg) without producing hepatotoxicity, by reducing ASO length (20-mer to 14-mer) and by employing novel ..
  75. ncbi Antisense pharmacodynamics: critical issues in the transport and delivery of antisense oligonucleotides
    R L Juliano
    Department of Pharmacology, University of North Carolina, Chapel Hill 27599, USA
    Pharm Res 16:494-502. 1999
    This review critically examines current understanding of the kinetics and biodistribution of antisense oligonucleotides, both at the cellular level and at the level of the intact organism...
  76. ncbi Identification of a cis-acting element for the regulation of SMN exon 7 splicing
    Hiroshi Miyajima
    Division of Structural Cellular Biology, Nara Institute of Science and Technology NAIST, 8916 5 Takayama, Ikoma, Nara 630 0101, Japan
    J Biol Chem 277:23271-7. 2002
    ..Mutations in element 1 or treatment with antisense oligonucleotides directed toward element 1 caused an increase in exon 7 inclusion...
  77. ncbi Structural requirements at the catalytic site of the heteroduplex substrate for human RNase H1 catalysis
    Walt F Lima
    Department of Molecular and Structural Biology, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA 92008, USA
    J Biol Chem 279:36317-26. 2004
    ..intra- and internucleotide phosphates are the crucial determinants in the selective recognition of the heteroduplex substrate by human RNase H1 and offer immediate steps to improve the performance of DNA-like antisense oligonucleotides.
  78. pmc Intracellular inhibition of hepatitis C virus (HCV) internal ribosomal entry site (IRES)-dependent translation by peptide nucleic acids (PNAs) and locked nucleic acids (LNAs)
    Christopher J Nulf
    Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390 9041, USA
    Nucleic Acids Res 32:3792-8. 2004
    ..IRES-directed inhibition of gene expression widens the range of mechanisms for antisense inhibition by PNAs and LNAs and may provide further therapeutic lead compounds for the treatment of HCV...
  79. ncbi Downregulation of human polo-like kinase activity by antisense oligonucleotides induces growth inhibition in cancer cells
    Birgit Spänkuch-Schmitt
    Department of Obstetrics and Gynecology, School of Medicine, JW Goethe University, Theodor Stern Kai 7, 60596 Frankfurt, Germany
    Oncogene 21:3162-71. 2002
    ..the role of PLK1 for mitotic progression of human cells and for neoplastic cell growth, phosphorothioate antisense oligonucleotides (ASOs) were tested to selectively downregulate PLK1 expression in MDA-MB-435 (breast cancer), HeLa S3 (..
  80. ncbi Zebrafish Foxd3 is required for development of a subset of neural crest derivatives
    James A Lister
    Department of Biological Structure and Center for Developmental Biology, University of Washington, HSB G514, Box 357420, Seattle, 98195 7420, USA
    Dev Biol 290:92-104. 2006
    ....
  81. ncbi Treatment of malignant gliomas with TGF-beta2 antisense oligonucleotides
    Peter Hau
    Department of Neurology, University of Regensburg, Medical School, Regensburg, Germany
    Expert Rev Anticancer Ther 9:1663-74. 2009
    ....
  82. ncbi Antisense treatments for biothreat agents
    Kelly L Warfield
    U S Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
    Curr Opin Mol Ther 8:93-103. 2006
    ....
  83. ncbi Antisense oligonucleotides as innovative therapeutic strategy in the treatment of high-grade gliomas
    Gerardo Caruso
    Neurosurgical Clinic, Department of Neurosciences Psychiatry and Anaesthesiology, University of Messina School of Medicine, Messina, Italy
    Recent Pat CNS Drug Discov 5:53-69. 2010
    ..b>Antisense oligonucleotides are synthetic stretches of DNA which hybridize with specific mRNA strands...
  84. ncbi Phase I trial of ISIS 104838, a 2'-methoxyethyl modified antisense oligonucleotide targeting tumor necrosis factor-alpha
    K Lea Sewell
    Isis Pharmaceuticals Inc, Carlsbad, California 92008 7208, USA
    J Pharmacol Exp Ther 303:1334-43. 2002
    ..The pharmacokinetics support an infrequent dosing interval. Inhibition of TNF-alpha production ex vivo was demonstrated...
  85. ncbi Application of ultrasonic gas-filled liposomes in enhancing transfer for breast cancer-related antisense oligonucleotides: an experimental study
    Yu kun Luo
    Department of Ultrasound, General Hospital of PLA, Beijing, China
    J Liposome Res 18:341-51. 2008
    ..the application of ultrasonic gas-filled liposomes in enhancing transfer for breast cancer-related antisense oligonucleotides in vitro...
  86. ncbi Antitumor effect of G3139 Bcl-2 antisense oligonucleotide is independent of its immune stimulation by CpG motifs in SCID mice
    Volker Wacheck
    Department of Clinical Pharmacology, Section of Experimental Oncology Molecular Pharmacology, University of Vienna, A 1090 Vienna, Austria
    Antisense Nucleic Acid Drug Dev 12:359-67. 2002
    ....
  87. ncbi Synthesis of antisense oligonucleotides containing 2'-O-psoralenylmethoxyalkyl adenosine for photodynamic regulation of point mutations in RNA
    Maiko Higuchi
    Department of Biomolecular Engineering, Kyoto Institute of Technology, Matsugasaki, Kyoto 606 8585, Japan
    Bioorg Med Chem 17:475-83. 2009
    ..Among them, 2'-Ps-eom exhibited superior photo-cross-linking efficiency with high sequence selectivity...
  88. pmc Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding
    Michelle L McWhorter
    Center for Molecular Neurobiology, The Ohio State University, Columbus, OH 43210, USA
    J Cell Biol 162:919-31. 2003
    ..These results show for the first time, in vivo, that Smn functions in motor axon development and suggest that these early developmental defects may lead to subsequent motoneuron loss...
  89. ncbi Neutrally charged phosphorodiamidate morpholino antisense oligomers: uptake, efficacy and pharmacokinetics
    Vikram Arora
    Research and Development, AVI BioPharma, Inc, USA
    Curr Pharm Biotechnol 5:431-9. 2004
    ..The sequencing of the human genome has greatly increased the potential of this approach. Antisense oligonucleotides, the most commonly used antisense approach, are unmodified or chemically modified single stranded RNA or ..
  90. ncbi Inhibition of HIV-1 Tat-dependent trans activation by steric block chimeric 2'-O-methyl/LNA oligoribonucleotides
    A Arzumanov
    Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 2QH, UK
    Biochemistry 40:14645-54. 2001
    ..An alternating PS-containing 3'-FAM OMe 12-mer oligonucleotide exhibited partial inhibition of trans-activation activity, but this was correlated with a similar effect on control gene expression, suggesting nonspecific inhibition...
  91. ncbi Effective intracellular delivery of oligonucleotides in order to make sense of antisense
    Fuxin Shi
    Department of Membrane Cell Biology, Faculty of Medical Sciences, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
    J Control Release 97:189-209. 2004
    For more than two decades, antisense oligonucleotides (ODNs) have been used to modulate gene expression for the purpose of applications in cell biology and for development of novel sophisticated medical therapeutics...
  92. ncbi Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing
    Jens Harborth
    Department of Biochemistry and Cell Biology, Max Planck Institute for Biophysical Chemistry, D 37077 Gottingen, Germany
    Antisense Nucleic Acid Drug Dev 13:83-105. 2003
    ....
  93. ncbi The inhibition of angiogenesis by antisense oligonucleotides to clusterin
    John K Jackson
    Faculty of Pharmaceutical Sciences, Vancouver, British Columbia, Canada
    Angiogenesis 8:229-38. 2005
    ..Clinical trials using antiangiogenic antisense oligonucleotides (aso's) for the treatment of ocular disorders or cancer are well advanced...
  94. ncbi LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA
    Birte Vester
    Nucleic Acid Center, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense
    Biochemistry 43:13233-41. 2004
    ..The wide applicability of LNA oligonucleotides for gene silencing and their use for research and diagnostic purposes are documented in a number of recent reports, some of which are described herein...
  95. ncbi Coordination of BMP-3b and cerberus is required for head formation of Xenopus embryos
    Jun Hino
    Department of Biochemistry, National Cardiovascular Center Research Institute, Suita, Osaka 565 8565, Japan
    Dev Biol 260:138-57. 2003
    ..These results revealed that xBMP-3b and cerberus are essential for head formation regulated by the Spemann organizer, and that xBMP-3b and perhaps xBMP-3 are involved in the axial patterning of Xenopus embryos...
  96. ncbi Antisense oligonucleotides targeted against glucocorticoid receptor reduce hepatic glucose production and ameliorate hyperglycemia in diabetic mice
    Yin Liang
    Endocrine Therapeutic and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, LLC Raritan, NJ 08869, USA
    Metabolism 54:848-55. 2005
    ..Our results demonstrate that selective inhibition of GCCR expression in the liver by the ASO-GCCR treatment reduced hepatic glucose production and improved blood glucose control under diabetic conditions...
  97. pmc Activating the synthesis of progerin, the mutant prelamin A in Hutchinson-Gilford progeria syndrome, with antisense oligonucleotides
    Loren G Fong
    Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Hum Mol Genet 18:2462-71. 2009
    ..Here, we show that antisense oligonucleotides (ASOs) against exon 11 sequences downstream from the exon 11 splice donor site promote alternate ..
  98. pmc Targeted intracellular delivery of antisense oligonucleotides via conjugation with small-molecule ligands
    Osamu Nakagawa
    Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 1072 Genetic Medicine Building, Chapel Hill, North Carolina 27599, USA
    J Am Chem Soc 132:8848-9. 2010
    ..Significant biological effects were attained in the sub-100 nM concentration range...
  99. ncbi Downregulation of Sirt1 by antisense oligonucleotides induces apoptosis and enhances radiation sensitization in A549 lung cancer cells
    Yuning Sun
    Beijing Institute of Radiation Medicine, 27 Taiping Road, Hai Dian District, Beijing 100850, China
    Lung Cancer 58:21-9. 2007
    ..The purpose of this study was to determine whether inhibition of Sirt1 by using antisense oligonucleotides (ASODN) induces apoptosis and enhances radiation sensitization in A549 lung cancer cells...
  100. ncbi Intravesical combination treatment with antisense oligonucleotides targeting heat shock protein-27 and HTI-286 as a novel strategy for high-grade bladder cancer
    Yoshiyuki Matsui
    The Prostate Centre at Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada
    Mol Cancer Ther 8:2402-11. 2009
    ..In this study, we show promising efficacy of intravesical combination treatment using antisense oligonucleotides targeting heat shock protein-27 (Hsp27; OGX427) with HTI-286, a synthetic analogue of the marine sponge ..
  101. pmc Biological barriers to therapy with antisense and siRNA oligonucleotides
    R Juliano
    UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Mol Pharm 6:686-95. 2009
    ..An understanding of the biological processes underlying these barriers will aid in the design of more effective delivery systems...

Research Grants70

  1. Reactive (AA)Amyloidosis
    Merrill D Benson; Fiscal Year: 2013
    ..model of AA amyloidosis to test the hypothesis that reduction of hepatic synthesis of SAA by specific antisense oligonucleotides (ASO) can reduce SAA and stop progression of amyloid fibril formation by limiting availability of AA ..
  2. Novel Collagen II Alternative Transcripts and Mouse Skeletal Development
    Audrey McAlinden; Fiscal Year: 2010
    ..chondrogenic differentiation when treated with insulin (ATDC5) we will transfect these cells with antisense oligonucleotides that will block splicing at the IIC splice site...
  3. Regulation of TGF-beta Signaling and Embryonic Development by GTPases
    Gerald H Thomsen; Fiscal Year: 2010
    ..Blocking endogenous GTPBP 1 or 2 in developing embryos with antisense oligonucleotides disrupts mesoderm differentiation, body patterning and organogenesis...
  4. The bioorganic chemistry of RNA editing by ADARs
    Peter A Beal; Fiscal Year: 2013
    ..Methods for site-selective inhibition of RNA editing will be developed. Backbone modified antisense oligonucleotides and helix- threading peptoids that target RNA editing substrates will be investigated for this purpose...
  5. Mechanisms of Lipid-Induced Hepatic Insulin Resistance
    Gerald I Shulman; Fiscal Year: 2013
    ..mice as well as awake rats with liver specific knockdown expression of INDY utilizing mRNA selective antisense oligonucleotides. INDY encodes a non-electrogenic dicarboxylate and citrate transporter and has been shown to promote ..
  6. A Comparative Approach to Globin Regulation/Thalassemia
    LEONARD IRA ZON; Fiscal Year: 2012
    ..The technology of morpholinos in which antisense oligonucleotides against specific genes are injected into the one cell embryo can knock-down gene function and will ..
  7. Antisense oligonucleotides for the treatment of spinocerebellar ataxia type 2
    Daniel R Scoles; Fiscal Year: 2013
    ..Our objective is identification of antisense oligonucleotides (ASOs) that lower ATXN2 expression...
  8. Neuron-specific block of T-type calcium channels
    Edward Perez-Reyes; Fiscal Year: 2012
    ..2 directed antisense oligonucleotides reverse the mechanical hyperalgesia and allodynia observed in these animals. Importantly, Cav3...
  9. Nicotinamide N-methyltransferase (NNMT) in obesity and insulin resistance
    Qin Yang; Fiscal Year: 2013
    ..Knockdown of NNMT with antisense oligonucleotides (ASO) in adipose tissue and liver of mice fed a high fat diet induces expression of spermine/spermidine ..
  10. Mechanisms of Perchlorate-Induced Disruption of Sexual Differentiation
    FRANK ARTHUR VON HIPPEL; Fiscal Year: 2013
    ..This research will advance our understanding of human thyroid diseases and the recent epidemic of impaired human reproductive health. ..
  11. Role of Splicing Factors in Breast Cancer
    OLGA ANCZUKOW-CAMARDA; Fiscal Year: 2013
    ..in the K99 phase and leading into the R00 phase, I will determine the therapeutic potential of using antisense oligonucleotides to modulate specific oncogenic alternative splicing events identified in Aims 1-3...
  12. Novel Nanopolymers to Inhibit Angiogenesis and Increase the Anti-tumor Immunity
    Manuel L Penichet; Fiscal Year: 2013
    ..receptor (TfR) monoclonal antibody for delivery through the endothelial system of the tumor vasculature, antisense oligonucleotides (AON) to inhibit angiogenesis, and/or potent immunostimulatory antibody-cytokine fusion proteins ..
  13. Therapeutic Development for Amyotrophic Lateral Sclerosis in a Canine Model
    JOAN RIPLEY COATES; Fiscal Year: 2013
    ..A promising therapeutic strategy using antisense oligonucleotides (ASOs) that target SOD1 mRNA to suppress SOD1 protein was recently demonstrated in a rodent ALS model...
  14. Role of Calcium-Activated Chloride Channels in Airway Disease Phenotypes
    ANAND CHAMPAK PATEL; Fiscal Year: 2011
    ..airway disease phenotypes driven by viral infection or allergen challenge, using AAV vectors to deliver antisense oligonucleotides that selectively inhibit mClca gene expression...
  15. Novel RNAi therapy for ALS and other Neurodegenerative Disorders
    Lyn Libertine; Fiscal Year: 2011
    ..In these mice, suppression of expression of the transgene using either antisense oligonucleotides or siRNA slows progression and improves survival...
  16. microRNA Uncoupling of Protein and Transcript Expression in Liver Regeneration
    CLIFFORD JOHN STEER; Fiscal Year: 2010
    ..Knockdown of Dicer or Ago2 will be carried out in vivo using siRNAs, antisense oligonucleotides or plasmid-based expression-systems...
  17. Role of the Bradykinin Pathway in Craniofacial Development
    LAURA ANNE JACOX; Fiscal Year: 2013
    ..These hypotheses will be tested after local loss of CPN function using antisense oligonucleotides and a face transplant assay developed in the Sive lab...
  18. Stimulated by Retinoic Acid (STra6) in Energy Homeostasis
    LAURA H ZEMANY; Fiscal Year: 2013
    ..insulin sensitivity, body composition, and energy expenditure will be studied in mice treated with STRA6 antisense oligonucleotides and in the adipose tissue STRA6 knockout mouse...
  19. Antisense oligonucleotide treatment for myotonic dystrophy
    Charles A Thornton; Fiscal Year: 2013
    ..To this end, we are proposing to develop RNase H-active antisense oligonucleotides (ASOs) targeting the mutant human DMPK {mut-hDMPK) mRNA...
  20. Changing tau Protein Levels and tau Protein Isoforms in Mouse Models of Dementia
    Timothy M Miller; Fiscal Year: 2012
    ..Building on prior experience using antisense oligonucleotides to down regulate genes in the brain and spinal cord, Dr...
  21. Exosome based therapeutics in Huntington's disease
    Neil Aronin; Fiscal Year: 2013
    ..expression of mutant huntingtin mRNA;this therapeutic can be accomplished in HD mouse models by siRNA, antisense oligonucleotides (ASO) and adeno-associated virus (AAV) with shRNAmir directed against huntingtin mRNA...
  22. Mechanisms Underlying Tauopathy Following Traumatic Brain Injury
    David Brody; Fiscal Year: 2013
    ..We propose for our third aim to create antisense oligonucleotides specifically targeting each type of JNK...
  23. Social and Motivational Properties of Vasoactive Intestinal Polypeptide Circuits
    James L Goodson; Fiscal Year: 2013
    ..1 will employ central antagonism of VIP receptors and site-specific knockdown of VIP production using antisense oligonucleotides to examine effects on sociality, anxiety, nesting, and parental care in male and female zebra finches...
  24. Assembly and Secretion of ApoB Containing Lipoproteins
    Henry N Ginsberg; Fiscal Year: 2013
    ..g., inhibition of apoB synthesis using antisense oligonucleotides (ASO)...
  25. Identification of Enhancers of Therapeutic Exon Skipping for DMD
    MELISSA JAN SPENCER; Fiscal Year: 2010
    ..Areas of interest include ..., methods for editing gene products in vivo, such as exon-skipping antisense oligonucleotides and small RNAs...
  26. Defining Target Contribution to Orofacial Pain by Antisense Oligonucleotides
    Zhigang Luo; Fiscal Year: 2009
    ..In this Competitive Revision, we plan to test if nanoparticle encapsulated antisense oligonucleotides against the Cava2d1 and TSP4 mRNA better efficacy than free antisense oligonucleotides in reversing ..
  27. Vitamin D Analogs as Adjuvants in Chemotherapy of Cancer
    George P Studzinski; Fiscal Year: 2013
    ..accomplished by a variety of approaches, including addition to cultured cells of pharmacological agents, antisense oligonucleotides, siRNAs, molecular decoys, and transfected plasmid constructs to study the molecular consequences of ..
  28. Macrophage Produced Phospholipid Transfer Protein (PLTP)
    Linda K Curtiss; Fiscal Year: 2012
    ..This will be accomplished with in vivo administration of mouse PLTP antisense oligonucleotides (ASO)...
  29. Hematopoietic regulation through Ott1-dependent alternative splicing
    Glen D Raffel; Fiscal Year: 2013
    ..The comprehensive strategy utilizing genetic complementation, chemical inhibitors, and antisense oligonucleotides to target the pathways regulating c-Mpl alternative splicing in this proposal may identify novel ..
  30. Characterizing an AMPA Receptor Splice Modulator in Preventing Epileptogenesis
    Melanie K Tallent; Fiscal Year: 2012
    ..Splice modulating oligonucleotides (SMOs) have unique chemistries and distinct advantages over classic antisense oligonucleotides and siRNA, and are in clinical trials for treating muscular dystrophy and spinal muscular atrophy...
  31. SMA mouse models: splicing manipulation and therapeutic SMN replacement
    CATHERINE DOMINGUEZ; Fiscal Year: 2013
    ..that we will be able to create an intermediate SMA mouse model from our current mild model, by using antisense oligonucleotides (ASO) to decrease the number of full-length proteins from the mutated Smn locus...
  32. Mouse Models to Define Critical Periods and Molecular Targets in FXTAS
    Robert F Berman; Fiscal Year: 2013
    ..Finally, we will use these mouse models to test novel treatment strategies using gapmer antisense oligonucleotides (AONs) that may improve neurological function in symptomatic carriers of the PM and in patients with ..
  33. Tumor-targeted silencing of Bcl-2/Bcl-xL by the self-assembled siRNA-nanovectors
    Liang Xu; Fiscal Year: 2010
    ..Successfully carried out, our studies will provide proof-of-concept that siRNA can be delivered by the self-assembled nanovectors for tumor-targeted silencing of the genes critical for cancer progression and resistance. ..
  34. Circadian Modulation of Drug-Seeking Behavior
    Heiko T Jansen; Fiscal Year: 2011
    ..Aim 3 will use antisense oligonucleotides injected in the SCN and VTA to assess the influence of clocks in these regions on time-of-day variation ..
  35. Targeting apoptosis via chemical design of Bcl-2 antagonists
    Maurizio Pellecchia; Fiscal Year: 2013
    ..Already, Bcl-2- targeting antisense oligonucleotides (GenasenseTM) are in Phase III clinical trials for melanoma and chronic lymphocytic leukemia (CLL), a ..
  36. RNA-mediated Mechanisms in the Myotonic Dystrophies
    Charles A Thornton; Fiscal Year: 2011
    ..We propose a novel use of antisense oligonucleotides, namely, to bind to CUGexp RNA and displace sequestered proteins, thereby releasing these proteins to ..
  37. p75NTR-Ceramide Signaling in Alzheimer?s Disease
    Luigi Puglielli; Fiscal Year: 2012
    ..whereas the genetic approaches include mutant neuronal cell lines, deletion mutant clones of p75NTR, antisense oligonucleotides, siRNA, and deletion mutants of p75SMI...
  38. The Pathogenesis of RNA Splicing Factor RP
    Eric A Pierce; Fiscal Year: 2013
    ..This approach has shown promise for treating muscular dystrophy in vivo, including a report of efficacy in a small clinical trial. ..
  39. Screening Assays for Small Molecules Targeting Oncogenic eIF4E Expression
    Chunhong Yan; Fiscal Year: 2013
    ..Indeed, eIF4E antisense oligonucleotides have been shown to inhibit tumor growth without toxicity to host animals, and have entered clinical ..
  40. A Large Animal Model of SMA
    Monique A Lorson; Fiscal Year: 2013
    ..The rapid and progressive postnatal phenotype makes it difficult to evaluate compounds and antisense oligonucleotides (ASOs) and to deliver and achieve expression of virally delivered therapeutics before the phenotype is ..
  41. Allele-Selective Inhibitors for Expanded Trinucleotide Repeat Genes
    David R Corey; Fiscal Year: 2013
    ..b>Antisense oligonucleotides (ASOs) or duplex RNAs can inhibit expression of trinucleotide repeat genes in animal models, but ..
  42. Pediatric toxicity and efficacy in long-term systemic treatment with anti-sense
    JOHANNES NICOLAAS VAN DEN ANKER; Fiscal Year: 2013
    ..A kidney toxicology assessment core supports these projects. ..
  43. Aging and Alzheimer's Disease Potential Link with IGF1-R
    Luigi Puglielli; Fiscal Year: 2012
    ..includes in vitro-assays and pharmacologic inhibitors, whereas the genetic approach includes siRNA, antisense oligonucleotides, and dominant mutants of the targeted signaling molecules...
  44. ALS/FTD mutant C9orf72-induced genetic and nuclear pathology in iPS cell models
    Rita Sattler; Fiscal Year: 2013
    ..Finally we will determine if we can abrogate C9orf72 genomic toxicity and pathology with antisense oligonucleotides already designed and validated in our laboratory...
  45. Enhancer Therapy
    Christopher K Glass; Fiscal Year: 2013
    ..Our goal is to directly test the novel idea that inhibition of eRNA expression can result in a therapeutic outcome, thereby establishing a transformative approach to treatment of human disease. ..
  46. STUDYING THE ROLE OF INFLAMMATORY MEDIATOR MIR-155 IN A MOUSE MODEL OF ALS
    ERICA DANIELLE KOVAL; Fiscal Year: 2013
    ..Finally, in Aim 3, we will knock down miR-155 with antisense oligonucleotides delivered directly into the cerebral spinal fluid with osmotic pump technology...
  47. ZFIN: The Zebrafish Model Organism Database
    Monte Westerfield; Fiscal Year: 2010
    ..study gene function by generating transgenic zebrafish or by knocking down gene function with morpholino antisense oligonucleotides. The functions of many of these genes are conserved among vertebrate groups...
  48. Small Molecule Screens to Identify Probes for Studies of Repair and Regeneration
    Andreas Vogt; Fiscal Year: 2013
    ..the study of signaling pathways to early development, when gene products can be knocked-down with antisense oligonucleotides. The objective of this proposal is to identify novel small molecule modulators of the FGF and TGFb ..
  49. Lung radioprotection by inhibition of TNF-alpha and TGF-beta1
    Ming Zhang; Fiscal Year: 2012
    ..we propose to block actions for both TGF-beta1 and TNF-alpha, a pathway that we previously demonstrated be crucial in radiation lung toxicity, by using specific antisense oligonucleotides to achieve improved lung radioprotection.
  50. Small molecule inhibitors of LMPTP: an obesity drug target
    Nunzio Bottini; Fiscal Year: 2013
    ..Recent in vivo data obtained using antisense oligonucleotides showed that knockdown of LMPTP reverses insulin resistance and lipid abnormalities in obese mice...
  51. Oligonucleotides for turning genes on and off with light
    IVAN JULIAN DMOCHOWSKI; Fiscal Year: 2012
    ..This will build on successful in vivo experiments in the PI's lab using light-activated antisense oligonucleotides. In Aim 1, we will develop two complementary methods for down-regulating gene expression with light ..
  52. Supporting RNAstructure: Software for RNA Analysis
    David H Mathews; Fiscal Year: 2013
    ..Furthermore, they can be used to design novel therapeutics, such as antisense oligonucleotides or small interfering RNA that both target RNA...
  53. ZFIN: The Zebrafish Model Organism Database
    Monte Westerfield; Fiscal Year: 2013
    ..study gene function by generating transgenic zebrafish or by knocking down gene function with morpholino antisense oligonucleotides. The functions of many of these genes are conserved among vertebrate groups...
  54. Correction of Hearing and Vestibular Defects in a Mouse Model for Deafness
    Michelle L Hastings; Fiscal Year: 2013
    ..In this project, we investigate the use of antisense oligonucleotides (ASOs) for the treatment of Usher syndrome in mice...
  55. CRP, Diabetes, Atherothrombosis
    Ishwarlal Jialal; Fiscal Year: 2010
    ..elucidate the molecular mechanism (s) by which CRP exerts these effects by employing in-vivo siRNA and antisense oligonucleotides to the different pathways identified...
  56. Modulation of VEGF-A alternative splicing as new anti-angiogenic therapeutics
    Zefeng Wang; Fiscal Year: 2013
    ..As a complementary approach, we will use antisense oligonucleotides (ASOs) to shift the VEGF-A splicing toward anti-antigenic isoforms...
  57. Analysis of HSCR patient exome sequence data using Zebrafish
    Iain T Shepherd; Fiscal Year: 2013
    ..This will benefit patients directly when they undergo genetic screening for the condition and will potentially offer scientists new targets for the development of novel therapies to treat HSCR. ..
  58. Spinal Muscular Atrophy: inducing SMN expression
    CHRISTINE DIDONATO; Fiscal Year: 2013
    ..It also addresses an unmet need in therapy development and provides insight to the underlying cellular mechanism of disease. ..
  59. Differential regulation of multiple transgenes for treatment of eye disease
    RICHARD J contact SAMULSKI; Fiscal Year: 2010
    ..In our regulation system, transgene expression is controlled by using antisense oligonucleotides targeting alternative splice site to modulate the alternative splicing of transgene message...
  60. Aptamer-Based Nanotechnology for Detection of Plasma Melanoma Markers
    Gary A Clawson; Fiscal Year: 2010
    ..The platform is being constructed in "bottom-up" fashion, and we have shown that NWs derivatized with antisense oligonucleotides fully retain their functionality after integration on chip...
  61. Bile acid-induced colon cancer cell proliferation
    Jean Pierre Raufman; Fiscal Year: 2009
    ..of EGFR will be confirmed by examining EGFR phosphorylation and by using EGFR inhibitors, antisense oligonucleotides, and dominant negative mutants.2...
  62. The Aryl Hydrocarbon Receptor as a New Therapeutic Target for Cancer
    Daniel C Koch; Fiscal Year: 2012
    ..AhR expression will be suppressed by AhR antisense oligonucleotides and/or shRNA to determine the requirement of AhR for growth inhibition in cancer cells Aim 2: Determine ..
  63. Tumor drug delivery systems based on polymalic acid
    Julia Y Ljubimova; Fiscal Year: 2010
    ..xenografted human brain tumors after a limited number of treatments with Polycefin bearing Morpholino antisense oligonucleotides to chains of vascular tumor protein, laminin-8 showed significantly increased survival (p<0...
  64. Regulation and function of Nurr1 in adult nigrostriatal dopamine neurons
    JEFFREY EELLS; Fiscal Year: 2009
    ..dopamine synthesis and changes in dopamine neuron survival in conditions of attenuated Nurr1 expression (antisense oligonucleotides and aging in Nurr1-null heterozygous mice)...
  65. ADHESION MOLECULES AND EPIDERMAL STRATIFICATION
    ROBERT LAVKER; Fiscal Year: 2001
    ..alternative approach, a more subtle way to block individual desmogleins, of which there are three, using antisense oligonucleotides will be attempted...
  66. MOLECULAR MECHANISMS OF HYDROCARBON/DNA INTERACTIONS
    William Baird; Fiscal Year: 1999
    ..in the metabolic activation of DB{alpha,l}P and BaP by Western blotting, inhibitory antibodies and antisense oligonucleotides. 3) To measure repair of individual BaP-, DMBA-, and DB[alpha,l]P-DNA addicts in human and rat mammary ..
  67. CHIRAL PHOSPHORUS LIGANDS AND ANTISENSE OLIGONUCLEOTIDES
    William Hersh; Fiscal Year: 1999
    ..The method should be equally applicable to the methylphosphonate and mixed backbone oligonucleotides. Such chiral nuclease-resistant oligonucleotides can in principle be highly gene-selective pharmaceutical reagents. ..
  68. INSULIN RESISTANCE AND CARDIOVASCULAR RISK FACTORS
    Brent Egan; Fiscal Year: 2004
    ..and activation of extracellular signal-regulated kinases in human aortic smooth muscle cells by using antisense oligonucleotides to specific PKCs...
  69. EXPERIMENTAL THERAPEUTICS EXPLOITING FOLATE RECEPTORS
    ASOK ANTONY; Fiscal Year: 2002
    ..the synthesis of FR in cultured HeLa-IU1 cells by introducing antisera to the purified trans-factor and antisense oligonucleotides to the cis-element into cells via F and determining if quenching FR (under conditions when FR expression ..
  70. HOMEOBOX GENES AND CONGENITAL MALFORMATION OF THE LUNG
    MaryAnn Volpe; Fiscal Year: 2002
    ..embryonic mouse lung cultures, Hoxb-5 expression will be stimulated with retinoic acid or inhibited with antisense oligonucleotides. Airway branching patterns and terminal bud counts will be measured...