This volume concentrates on the most relevant oligonucleotide research and drug development areas and emphasizes the basic mechanisms and biology of oligonucleotide reagents.Chapters are devoted to RNAi, oligonucleotide delivery, and immunomodulation. Because of the advanced stages of oligonucleotide-based drug development, preclinical and clinical data are also presented by leaders in the field.NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit www.blackwellpublishing.com/nyas.ACADEMY MEMBERS: Please contact the New York Academy of Sciences directly to place your order (www.nyas.org). Members of the New York Academy of Science receive full-text access to the Annals online and discounts on print volumes. Please visit www.nyas.org/membership/main.asp for more information about becoming a member.

Thomas Tuschl is a German biochemist and molecular biologist, known for his research on RNA. John J. Rossi is the editor of Oligonucleotide Therapeutics: First Annual Meetingof the Oligonucleotide Therapeutics Society, Volume 1082, published by Wiley.

Preface and Overview.

By THOMAS TUSCHL AND JOHN ROSSI

xi

Part I. Delivery

Surface-Modified LPD Nanoparticles for Tumor Targeting.

By SHYH-DAR LI AND LEAF HUANG

1

Atelocollagen-Mediated Systemic DDS for Nucleic Acid Medicines.

By KOJI HANAI, FUMITAKA TAKESHITA, KIMI HONMA, SHUNJI NAGAHARA, MIHO MAEDA, YOSHIKO MINAKUCHI, AKIHIKO SANO, AND TAKAHIRO OCHIYA

9

Intracellular Delivery of Oligonucleotide Conjugates and Dendrimer Complexes.

By R.L. JULIANO

18

Mechanism of PNA Transport to the Nuclear Compartment.

By LENKA STANKOVA, AMY J. ZIEMBA, ZHANNA V. ZHILINA, AND SCOT W. EBBINGHAUS

27

Part II. Identifying and Validating Targets and Systems

TLR9 and the Recognition of Self and Non-Self Nucleic Acids.

By MARC S. LAMPHIER, CHERILYN M. SIROIS, ANJALI VERMA, DOUGLAS T. GOLENBOCK, AND EICKE LATZ

31

RNA Silencing in the Struggle against Disease.

By VOLKER PATZEL, ISABELL DIETRICH, AND STEFAN H.E. KAUFMANN

44

Cellular Dynamics of Antisense Oligonucleotides and Short Interfering RNAs.

By LI KIM LEE, BRANDEE M. DUNHAM, ZHUTING LI, AND CHARLES M. ROTH

47

Inhibition of Hepatitis C IRES-Mediated Gene Expression By Small Hairpin RNAs in Human Hepatocytes and Mice.

By HEINI ILVES, ROGER L. KASPAR, QIAN WANG, ATTILA A. SEYHAN, ALEXANDER V. VLASSOV, CHRISTOPHER H. CONTAG, DEVIN LEAKE, AND BRIAN H. JOHNSTON

52

SiRNA-Mediated Selective Inhibition of Mutant Keratin mRNAs Responsible for the Skin Disorder Pachyonychia Congenita.

By ROBYN P. HICKERSON, FRANCES J.D. SMITH, W.H. IRWIN MCLEAN, MARKUS LANDTHALER, RUDOLF E. LEUBE, AND ROGER L. KASPAR

56

Multitargeted Approach Using Antisense Oligonucleotides for the Treatment of Asthma.

By Z. ALLAKHVERDI, M. ALLAM, A. GUIMOND, N. FERRARI, K. ZEMZOUMI, R. SÉGUIN, L. PAQUET, AND P.M. RENZI

62

Therapeutic Modulation of DMD Splicing By Blocking Exonic Splicing Enhancer Sites with Antisense Oligonucleotides.

By A. AARTSMA-RUS, A.A.M. JANSON, J.A. HEEMSKERK, C.L. DE WINTER, G.-J.B. VAN OMMEN, AND J.C.T. VAN DEUTEKOM

74

Neuromuscular Therapeutics By RNA-Targeted Suppression of ACHE Gene Expression.

By AMIR DORI AND HERMONA SOREQ

77

Characterization of Antisense Oligonucleotides Comprising 2'-Deoxy-2'-Fluoro-β-D-Arabinonucleic Acid (FANA): Specificity, Potency, and Duration of Activity.

By NICOLAY FERRARI, DENIS BERGERON, ANNA-LISA TEDESCHI, MARIA M. MANGOS, LUC PAQUET, PAOLO M. RENZI, AND MASAD J. DAMHA

91

Anti-HIV Activity of Steric Block Oligonucleotides.

By GABRIELA IVANOVA, ANDREY A. ARZUMANOV, JOHN J. TURNER, SANDRINE REIGADAS, JEAN-JACQUES TOULMÉ, DOUGLAS E. BROWN, ANDREW M.L. LEVER, AND MICHAEL J. GAIT

103

Selection of Thioaptamers for Diagnostics and Therapeutics.

By XIANBIN YANG, HE WANG, DAVID W.C. BEASLEY, DAVID E. VOLK, XU ZHAO, BRUCE A. LUXON, LEE O. LOMAS, NORBERT K. HERZOG, JUDITH F. ARONSON, ALAN D.T. BARRETT, JAMES F. LEARY, AND DAVID G. GORENSTEIN

116

Modification of the Pig CFTR Gene Mediated By Small Fragment Homologous Replacement.

By ROSALIE MAURISSE, JUDY CHEUNG, JONATHAN WIDDICOMBE, AND DIETER C. GRUENERT

120

Part III. Clinical Studies

Nucleic Acid Therapeutics for Hematologic Malignancies Theoretical Considerations.

By JOANNA B. OPALINSKA, ANNA KALOTA, JYOTI CHATTOPADHYAYA, MASAD DAMHA, AND ALAN M. GEWIRTZ

124

CpG Oligonucleotides Improve the Protective Immune Response Induced By the Licensed Anthrax Vaccine.

By DENNIS M. KLINMAN, HANG XIE, AND BRUCE E. IVINS

137

Anti-VEGF Aptamer (Pegaptanib) Therapy for Ocular Vascular Diseases.

By EUGENE W.M. NG AND ANTHONY P. ADAMIS

151

RNAi in Combination with a Ribozyme and TAR Decoy for Treatment of HIV Infection in Hematopoietic Cell Gene Therapy.

By MINGJIE LI, HAITANG LI, AND JOHN J. ROSSI

172

Index of Contributors

181

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