Isis Pharmaceuticals, Inc.

Christopher K Mirabelli

David J Ecker

Stanley T Crooke

C Frank Bennett

Lex M Cowsert

Kenneth G Draper

Jacqueline R Wyatt

Brenda F Baker

Timothy A Vickers

Clarence Frank Bennett

Kevin P Anderson

Ronnie C Hanecak

Vickie L Brown-Driver

Debra L Robertson

Compositions and methods for the treatment of ophthalmic disorders, particularly preservation of corneal explants and prevention of corneal allograft rejection. These compositions comprise oligonucleotides which are specifically hybridizable with nucleic acids encoding the cellular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1).

Oligonucleotide modulation of cell adhesion

Compositions and methods are provided for the treatment and diagnosis of herpesvirus infections. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with RNA or DNA deriving from a gene corresponding to one of the open reading frames UL5, UL8, UL9, UL13, UL29, UL30, UL39, UL40, UL42 AND UL52 of herpes simplex virus type 1. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a translation initiation site; it is also preferred that they comprise the sequence CAT. Methods of treating animals suspected of being infected with herpesvirus comprising contacting the animal with an oligonucleotide specifically hybridizable with RNA or DNA deriving from one of the foregoing genes of the herpesvirus are disclosed. Methods for treatment of infections caused by herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, human herpes virus 6, Epstein Barr virus or varicella zoster virus are disclosed.

Oligonucleotide therapies for modulating the effects of herpesviruses

Compositions and methods are provided for the treatment and diagnosis of diseases amenable to treatment through modulation of the synthesis or metabolism of intercellular adhesion molecules. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5&prime;-untranslated sequences, 3&prime;-untranslated sequences, and intervening sequences. Methods of treating animals suffering from disease amenable to therapeutic intervention by modulating cell adhesion proteins with an oligonucleotide specifically hybridizable with RNA or DNA corresponding to one of the foregoing proteins are disclosed. Methods for treatment of diseases responding to modulation cell adhesion molecules are disclosed.

Oligonucleotide inhibition of cell adhesion

Antisense oligonucleotide inhibition of papillomavirus

Compositions and methods are provided for the treatment and diagnosis of diseases amenable to treatment through modulation of the synthesis or metabolism of intercellular adhesion molecules. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5&prime;-untranslated sequences, 3&prime;-untranslated sequences, and intervening sequences. Methods of treating animals suffering from disease amenable to therapeutic intervention by modulating cell adhesion proteins with an oligonucleotide specifically hybridizable with RNA or DNA corresponding to one of the foregoing proteins are disclosed. Methods for treatment of diseases responding to inhibition of cell adhesion molecules are disclosed.

Compositions and methods are provided for the modulation of expression of cellular adhesion molecules. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1. Methods of modulating expression of cellular adhesion molecules are provided, as are methods of treating conditions associated with cellular adhesion molecules. In a preferred embodiment, the cellular adhesion molecule is ICAM-1, and a preferred antisense sequence targeted to human ICAM-1 is demonstrated to have clinical utility in several disease indications.

Antisense modulation of cell adhesion molecule expression and treatment

Compositions and methods are provided for the treatment and diagnosis of diseases amenable to treatment through modulation of the synthesis or metabolism of intercellular adhesion molecules. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5'-untranslated sequences, 3'-untranslated sequences, and intervening sequences. Methods of treating animals suffering from disease amenable to therapeutic intervention by modulating cell adhesion proteins with an oligonucleotide specifically hybridizable with RNA or DNA corresponding to one of the foregoing proteins are disclosed. Methods for treatment of diseases responding to modulation cell adhesion molecules are disclosed.

Oligonucleotides and oligonucleotide analogs are provided which are capable of antisense interaction with messenger RNA of papillomavirus. Such oligonucleotides or oligonucleotide analogs can be used for diagnostics and therapeutics as well as for research purposes. In accordance with preferred embodiments of this invention, oligonucleotide or oligonucleotide analog is provided which is hybridizable with a messenger RNA from a papillomavirus. The oligonucleotide or oligonucleotide analog is able to inhibit the function of the RNA, and accordingly is useful for therapy for infections by such papillomavirus. In accordance with a preferred embodiment, portions of the papillomavirus are targeted for antisense attack. Thus oligonucleotides are preferably provided which hybridize with the E2, E1, E7, or E6-7 messenger RNAs.

Oligonucleotides for Papillomavirus

Oligonucleotides are provided which are targeted to human papillomavirus E2 transactivator messenger RNA. Such oligonucleotides can be used for diagnostics and therapeutics as well as for research purposes.

Oligonucleotides for the diagnosis of papillomavirus

Oligonucleotides are provided which are capable of antisense interaction with messenger RNA of papillomavirus. Such oligonucleotides or oligonucleotide analogs can be used for diagnostics and therapeutics as well as for research purposes. In accordance with preferred embodiments of this invention, oligonucleotides are provided which are hybridizable with selected messenger RNA from a human papillomavirus. The oligonucleotide is able to inhibit the function of the RNA, and accordingly is useful for therapy for infections by such papillomavirus. In accordance with a preferred embodiment, portions of the papillomavirus are targeted for antisense attack. Thus oligonucleotides are preferably provided which hybridize with the E2, E6 and E7 messenger RNAs.

Antisense oligonucleotides directed to papillomavirus

Antisense oligonucleotide inhibition of papillomavirus transformed cells

Compositions and methods are provided for the treatment and diagnosis of herpesvirus infections. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with RNA or DNA deriving from a gene corresponding to one of the open reading frames UL5, UL8, UL9, UL13, UL29, UL30, UL39, UL40, UL42 AND UL52 of herpes simplex virus type 1. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a translation initiation site; it is also preferred that they comprise the sequence CAT. Methods of treating animals suspected of being infected with herpesvirus comprising contacting the animal with an oligonucleotide specifically hybridizable with RNA or DNA deriving from one of the foregoing genes of the herpesvirus; are disclosed. Methods for treatment of infections caused by herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, human herpes virus 6, Epstein Barr virus or varicella zoster virus are disclosed.

Methods for identifying oligonucleotides having a desired activity in vivo are disclosed. In accordance with preferred embodiments, oligonucleotides capable of conferring a desired phenotype are identified. Therapeutic, diagnostic and research methods and compositions employing such oligonucleotides are provided. Prior knowledge of the sequence or structure of a target molecule is generally not required.

Growing community of inventors

Dover, MA, United States of America

Christopher K Mirabelli