Isis Pharmaceuticals, Inc.

Kevin P Anderson

Ronnie C Hanecak

Chikateru Nozaki

David J Ecker

Jacqueline R Wyatt

Kenneth G Draper

Thomas W Bruice

Timothy A Vickers

Vickie L Brown-Driver

C Frank Bennett

Fukusaburo Hamada

Hiroshi Nakatake

Tsukasa Nishihara

Tatsuo Eto

Kazuya Hoshiko

Shinichi Furukawa

Brenda F Baker

Walter F Lima

Peter W Davis

Ming-Yi Chiang

Susan M Freier

Phillip Dan Cook

Lex M Cowsert

Stanley T Crooke

Yogesh S Sanghvi

Christopher K Mirabelli

Shoji Furusako

Daniel L Kisner

Jean Louis Imbach

F Andrew Dorr

Shoji Furasako

T Jesse Kwoh

Sharon Chapman

Modified oligonucleotides having a GGG motif sequence and a sufficient number of flanking nucleotides to modulate the telomere length of a chromosome are provided. Methods of modulating telomere length of a mammalian chromosome in vitro and in vivo are also provided, as are methods for inhibiting the division of a malignant mammalian cell and for modulating the effects of cellular aging.

Modulation of telomere length by oligonucleotides having a G-core sequence

Antisense oligonucleotides are provided which are complementary to and hybridizable with at least a portion of HCV RNA and which are capable of inhibiting the function of the HCV RNA. These oligonucleotides can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus, and for diagnosis and detection of HCV and HCV-associated diseases. Methods of using these compounds are also disclosed.

Compositions and methods for treatment of hepatitis C virus-associated diseases

Antisense oligonucleotides are provided which are complementary to at least a portion of HCV RNA and specifically hybridizable therewith. These oligonucleotides can be administered to inhibit the replication of Hepatitis C virus in vivo or in vitro and to treat Hepatitis C virus-associated disease. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus.

Compositions and methods for treatment of Hepatitis C virus associated diseases

Compositions and methods for treatment of Hepatitis C virus-associated diseases

This invention concerns compositions and methods for the treatment of CMV infections. Antisense oligonucleotides are provided which are effective antiviral agents. In preferred embodiments, the oligonucleotides contain at least one 2'-methoxyethoxy modification and may be chimeric oligonucleotides.

Composition and method for treatment of CMV infections

Antisense oligonucleotides are provided which are capable of inhibiting HBV replication. These oligonucleotides are specifically hybridizable with HBV RNAs which encode a P gene product, S gene product or C gene product, or with the 5' cap region, U5 region, .epsilon. region or translation initiation site of HBV RNA. Methods of diagnosing HBV infection, methods of inhibiting HBV replication, methods of treating an HBV infection and methods of treating or preventing HBV-associated diseases using the oligonucleotides of the invention are also provided. Such diseases may include acute hepatitis, chronic hepatitis, fulminant hepatitis, or hepatocellular carcinoma.

Antisense inhibition of hepatitis B virus replication

Oligonucleotides having a conserved G4 core sequence

Compositions and methods are provided for inhibiting the translation of a capped target mRNA. Antisense oligomers of the invention are targeted to the 5' cap region of the target mRNA and include oligonucleosides, PNAs, or oligonucleotides modified at the 2' position of the sugar. Preferably said oligomers inhibit protein translation directly via interference with ribosome assembly.

Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2

Methods useful for the determination of oligomers which have specific activity for a target molecule from a pool of primarily randomly assembled oligomers are provided. The disclosed methods involve repeated syntheses of increasingly simplified sets of oligomers coupled with selection procedures for determining oligomers having the highest activity. Freedom from the use of enzymes allows the application of these methods to any molecules which can be oligomerized in a controlled fashion.

Methods for synthetic unrandomization of oligomer fragments

Synthetic unrandomization of oligomer fragments

Oligonucleotides for modulating the effects of cytomegalovirus infections

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Carlsbad, CA, United States of America

Kevin P Anderson