Abstract: Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2?-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.

Abstract: The present invention relates to regulation of lymphocyte activation. More particularly, the present invention is directed to nucleic acids encoding PAK2, which is involved in modulation of lymphocyte activation. The invention further relates to methods for identifying and using agents, including small organic molecules, peptides, circular peptides, antibodies, lipids, antisense nucleic acids, and ribozymes, that modulate lymphocyte activation via modulation of PAK2; as well as to the use of expression profiles and compositions in diagnosis and therapy related to lymphocyte activation and suppression.

Abstract: Therapeutic agents which target heat shock protein (hsp) 27 in vivo are used to provide treatment to individuals, particularly human individuals, suffering from prostate cancer and other cancers that overexpress hsp27. A therapeutic agent, for example an antisense oligonucleotide or RNAi nucleotide inhibitor with sequence specificity for hsp27 mRNA, for example human hsp27 mRNA, is administered to an individual suffering from prostate cancer or some other cancer expressing elevated levels of hsp 27 in a therapeutically effective amount. The therapeutic agent is suitably formulated into a pharmaceutical composition which includes a pharmaceutically acceptable carrier, and packaged in dosage unit form. A preferred dosage unit form is an injectable dosage unit form.

Abstract: The present invention is directed to novel peptides and compositions capable of modulating apoptosis in cells, and to methods of modulating apoptosis employing the novel peptides and compositions of the invention. In one aspect, the invention is directed to a novel peptide designated the “GD domain,” which is essential both to Bak's interaction with Bcl-xL, and to Bak's cell killing function. Methods of identifying agonists or antagonists of GD domain function are provided. The GD domain is responsible for mediating key protein/protein interactions of significance to the actions of multiple cell death regulatory molecules.

Abstract: The invention provides a method of decreasing human immunodeficiency virus entry into cells, the method comprising decreasing levels of functional CD63 present with the human immunodeficiency virus and the cells. The invention further provides a method of treating or preventing human immunodeficiency virus infection in a subject, the method comprising administering to the subject an amount of a compound effective to decrease levels of functional CD63 in the cells of the subject.

Abstract: Disclosed are diagnostic and prognostic kits for the detection and treatment of proliferative diseases such as ovarian cancer, breast cancer, and lymphoma. Also disclosed are cancer therapeutics utilizing IAP antisense nucleic acids IAP fragments, and antibodies which specifically bind IAP polypeptides.

Abstract: A method for altering transcription in a cell comprising an amount of active CDK9/cyclin, comprises the steps of: (a) introducing in the cell an agent which modulates the amount of active CDK9/cyclin in the cell, and thereby alters transcription in the cell, wherein the agent comprises an RNA selected from the group consisting of an RNA aptamer that specifically binds CDK9/cyclin, a CDK9/cyclin-binding domain of 7SK RNA, a 7SK RNA-binding antisense 7SK RNA domain, and a 7SK RNA-specific RNAi, and (b) detecting a resultant altering of transcription in the cell. Methods for screening for an agent which modulates 7SK RNA-CDK9/cyclin binding generally comprise the steps of (a) incubating a mixture of 7SK RNA, CDK9/cyclin and a candidate agent under conditions wherein but for the presence of the agent, the 7SK RNA and CDK9/cyclin engage in a reference binding; and (b) detecting an agent-biased binding of the 7SK RNA to the CDK9/cyclin.

Abstract: Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids. In general, the compounds are oligonucleotides which contain at least one region of 2?-modified nucleosides connected by alternating phosphodiester and phosphorothioate linkages.

Abstract: The invention provides compositions containing an effective amount of a therapeutic agent encapsulated in a liposome coupled to a desialyated glycoprotein, e.g., desialyated glycoprotein-?1. This invention further provides methods for the targeted delivery of a therapeutic agent to a tissue expressing asialoglycoprotein receptors by delivery to the tissue an effective amount of a composition containing an effective amount of the agent encapsulated in a liposome coupled to a desialyated glycoprotein, e.g., desialyated glycoprotein-?1. Also provided by this invention is a method for inhibiting the proliferation of liver cancer by administering to a subject in need of such therapy an effective amount of a composition containing doxorubicin encapsulated in desialyated glycoprotein-?1 coupled to a liposome.