Abstract: Compounds, compositions and methods are provided for modulating the expression of glucagon receptor. The compositions comprise oligonucleotides, targeted to nucleic acid encoding glucagon receptor. Methods of using these compounds for modulation of glucagon receptor expression and for diagnosis and treatment of disease associated with expression of glucagon receptor are provided.

Abstract: Compositions and methods for the diagnosis, prevention and treatment of immune states and disorders amenable to treatment through modulation of T cell activation are provided. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding B7 proteins.

Abstract: An improved process for preparing 2'-O-substituted guanosine comprising reacting an unprotected 2,6-diaminopurine riboside with an alkyl halide in the presence of a sodium hydride or a base of equal strength followed by a deamination step with adenosine deaminase. Such modified guanosine molecules can be used to synthesize 2'-O-modified oligonucleotides. The above alkylating process can also be used to prepare 3'-O-alkyl- and 2',3'-di-O-alkyl-2,6-diaminopurine ribosides. The deamination of these nucleosides yields the corresponding guanosine derivatives.

Abstract: 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, oligonucleotide ISIS 2105 is provided which hybridizes 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.

Abstract: Crosslinked copolymers of N-vinylpyrrolidone and other n-vinyl-lactam monomers and ethylenically unsaturated monomer having at least one amine or amine-displaceable functionality are utilized for oligomer synthesis. The oligomer of interest is connected to the polymer via a connection to an amine function. A spacer can be included between the amine function and the polymeric backbone.

Abstract: Methods for preparing oligonucleotide analogs which have improved nuclease resistance and improved cellular uptake are provided. In preferred embodiments, the methods involve reductive coupling of 3'- and 4'-substituted or 4'- and 3'-substituted nucleosidic synthons.

Abstract: Oligonucleotide surrogates comprising a plurality of cyclobutyl moieties covalently joined by linking moieties are prepared and used as antisense diagnostics and research reagents. Methods of synthesis and use of both the oligonucleotide surrogates and intermediates thereof are disclosed.

Abstract: Compositions and methods for modulating the activity of RNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. In preferred embodiments, the reactive portions comprise one or two imidazole functionalities conjugated to the targeting oligonucleotide via linkers with and without intervening intercalating moieties and act through phosphorodiester hydrolytic bond cleavage. Therapeutics, diagnostics and research methods are also disclosed. Synthetic nucleosides and nucleoside fragments are also provided which are useful for elaboration of oligonucleotides for such purposes.

Abstract: Oligonucleotide analogs are provided having improved cellular uptake and improved nuclease resistance. Modification of oligonucleotides through the attachment of nitrogenous moieties, especially polyamines, hydrazines and the like to nucleosidic portions of the analogs is disclosed. Oligonucleotides targeted at the tat region of HIV comprise certain preferred embodiments.

Abstract: Sequence-specific oligonucleotides are provided having substantially pure chiral Sp phosphorothioate, chiral Rp phosphorothioate, chiral Sp alkylphosphonate, chiral Rp alkylphosphonate, chiral Sp phosphoamidate, chiral Rp phosphoamidate, chiral Sp phosphotriester, and chiral Rp phosphotriester linkages. The novel oligonucleotides are prepared via a stereospecific SN.sub.2 nucleophilic attack of a phosphodiester, phosphorothioate, phosphoramidate, phosphotriester or alkylphosphonate anion on the 3' position of a xylonucleotide. The reaction proceeds via inversion at the 3' position of the xylo reactant species, resulting in the incorporation of phosphodiester, phosphorothioate, phosphoramidate, phosphotriester or alkylphosphonate linked ribofuranosyl sugar moieties into the oligonucleotide.

Abstract: Oligonucleotide analogs are provided having improved cellular uptake and improved nuclease resistance. Modification of oligonucleotides through the attachment of nitrogenous moieties, especially polyamines, hydrazines and the like to nucleosidic portions of the analogs is disclosed. Oligonucleotides targeted at the tat region of HIV comprise certain preferred embodiments.