Abstract: Compositions and methods are provided for modulating the expression of bcl-x. Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding bcl-x are preferred. Methods of using these compounds for modulation of bcl-x expression and for treatment of diseases associated with expression of bcl-x are also provided. Methods of sensitizing cells to apoptotic stimuli are also provided.

Abstract: Compounds, compositions and methods are provided for modulating the expression of hypoxia-inducible factor 1 alpha. The compositions comprise oligonucleotides, targeted to nucleic acid encoding hypoxia-inducible factor 1 alpha. Methods of using these compounds for modulation of hypoxia-inducible factor 1 alpha expression and for diagnosis and treatment of disease associated with expression of hypoxia-inducible factor 1 alpha are provided.

Abstract: Provided are methods for lowering plasma lipid in an individual in need of or desirous of lowering plasma lipid by administering an amount of an exendin or an exendin agonist analog effective to lower plasma lipid.

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: Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2?-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2?-deoxy-2?-fluoro, 2?-O-methoxy, 2?-O-ethoxy, 2?-O-propoxy, 2?-O-aminoalkoxy or 2?-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3? or the 5? positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.

Abstract: Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2?-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2?-deoxy-2?-fluoro, 2?-O-methoxy, 2?-O-ethoxy, 2?-O-propoxy, 2?-O-aminoalkoxy or 2?-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3? or the 5? positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.

Abstract: Modified oligonucleotides containing both A-form conformation geometry and B-from conformation geometry nucleotides are disclosed. The B-form geometry allows the oligonucleotide to serve as substrates for RNase H when bound to a target nucleic acid strand. The A-form geometry imparts properties to the oligonucleotide that modulate binding affinity and nuclease resistance. By utilizing C2? endo sugars or O4? endo sugars, the B-form characteristics are imparted to a portion of the oligonucleotide. The A-form characteristics are imparted via use of either 2?-O-modified nucleotides that have 3? endo geometries or use of end caps having particular nuclease stability or by use of both of these in conjunction with each other.

Abstract: Methods for treating conditions or disorders which can be alleviated by reducing food intake are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist, alone or in conjunction with other compounds or compositions that affect satiety. The methods are useful for treating conditions or disorders, including obesity, Type II diabetes, eating disorders, and insulin-resistance syndrome. The methods are also useful for lowering the plasma glucose level, lowering the plasma lipid level, reducing the cardiac risk, reducing the appetite, and reducing the weight of subjects. Pharmaceutical compositions for use in the methods of the invention are also disclosed.

Abstract: Method for detecting and identifying unknown bioagents, including bacteria, viruses and the like, by a combination of nucleic acid amplification and molecular weight determination using primers which hybridize to conserved sequence regions of nucleic acids derived from a bioagent and which bracket variable sequence regions that uniquely identify the bioagent. The result is a “base composition signature” (BCS) which is then matched against a database of base composition signatures, by which the bioagent is identified.

Abstract: Compounds are provided containing purine nucleotides that bear moieties X at the 2? position thereof wherein X is R1—(R2)n; R1 is C3-C20 alkyl, C4-C20 alkenyl or C2-C20 alkynyl; R2 is halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides; and n is an integer from 0 to about 6. Such compounds are useful for modulating the synthesis of proteins.

Abstract: 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.

Abstract: A scalable process for purification of phosphorodiamidite includes steps of solubilizing a crude phosphorodiamidite in an apolar organic solvent, contacting the non-polar organic solvent with a polar phase comprising a polar organic solvent to remove impurities from the solubilized phosphorodiamidite, and removing the non-polar organic solvent from the phosphorodiamidite.

Abstract: Synthetic processes are provided wherein oligomeric compounds are prepared having phosphodiester, phosphorothioate, phosphorodithioate, or other covalent linkages. The oligomers have substantially reduced exocyclic adducts deriving from acrylonitrile or related contaminants.

Abstract: Nucleosides and oligonucleosides functionalized to include alkylamino functionality, and derivatives thereof. In certain embodiments, the compounds of the invention further include steroids, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleosides through the alkylamino group.

Abstract: A sequential support-bound synthesis method is disclosed for preparing a conjugated oligomeric compound, preferably a PNA-peptide conjugate or an oligonucleotide-peptide conjugate, using a bridging molecule having at least two N-protecting amino groups. A conjugated oligomeric compound for therapeutic or prophylactic delivery is also disclosed.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of MyD88. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding MyD88. Methods of using these compounds for modulation of MyD88 expression and for treatment of diseases associated with expression of MyD88 are provided.

Abstract: A laser drilling system forms an opening in the coating of a pharmaceutical dosage form and includes an orienting assembly to correctly orient dosage forms, a debris removal assembly to reduce buildup of and reduce exposure to drilling debris and a quality control assembly to verify that the opening formed conforms to predetermined specifications.

Abstract: A process of purifying phosphoramidite precursors useful in inter alia synthesis of oligonucleotides comprises dissolving a crude phosphoramidite in a polar phase, adding a basic compound to the polar phase, adding a portion of water to the polar phase, contacting the polar phase with a first apolar phase to extract impurity into the apolar phase, separating the first apolar phase from the polar phase, adding a second aliquot of water to the polar phase, and contacting the polar phase with a second apolar phase, whereby the phosphoramidite partitions into the second apolar phase.

Abstract: Oligonucleotides and other macromolecules are provided which have increased nuclease resistance, substituent groups for increasing binding affinity to complementary strand, and subsequences of 2?-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H. Such oligonucleotides and macromolecules are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics.

Abstract: Compounds having structure (1) wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.