Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: Provided herein are antisense oligonucleotides that can effectively prevent or decrease c-myc protein expression as well as decrease overall rates of cell proliferation in in vitro and mammalian in vivo models of cell proliferative disorders as well as methods for using the same.

Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2?-arabino-fluoronucleoside and an internucleoside 3?-NH—P(—O)(OR)—O-5? linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2?-arabino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.

Abstract: Compounds of the form O-(x-L)n, where O is an oligonucleoside having at least a plurality of N3??P5? thiophosphoramidate (NPS) internucleoside linkages, a conjugated lipid moiety L, and at least one G-rich sequence motif as described, are effective to morphologically alter and reduce adhesion of cancer cells.

Abstract: This invention relates to antisense oligonucleotides comprising at least one N3??P5? phosphorodiamidate linkage (NPN) in the backbone, and kits and pharmaceutical compositions thereof, useful for modulating gene expression involved in the pathogenesis of a disease. Also included are compounds useful as building blocks of said antisense oligonucleotides and methods of preparing said antisense oligonucleotides and building block compounds including NPN linkages.

Abstract: Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.

Abstract: Methods of reliably quantifying telomere length in cells or tissues that have been formalin fixed and paraffin embedded (FFPE) samples by quantitative polymerase chain reaction protocol and kits for use with such various methods are provided. The methods of the present invention may be used to predetermine an individual's response to treatment with a telomerase inhibitor, a telomere damaging agent or a telomerase activator.

Abstract: The invention provides methods for determining the susceptibility of cancer patients to developing adverse reactions if treated with a telomerase inhibitor drug by measurement of telomere length in appropriate cells of the patient prior to initiation of the telomerase inhibitor treatment.

Abstract: This invention relates to compounds useful for inhibiting telomere elongation. More specifically, the invention provides nucleotide analogs that are incorporated into telomeres by telomerase thereby inhibiting elongation of telomeres. The compounds are useful in treating cancer and other cell proliferative diseases.

Abstract: Oligonucleotide conjugates, where an oligonucleotide is covalently attached to an aromatic system, are provided. In particular embodiments the oligonucleotide is complementary to the RNA component of human telomerase and is covalently attached to a nucleobase via an optional linker. The conjugates inhibit telomerase enzyme activity.

Abstract: Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.

Abstract: Provided herein are methods for reducing neoplastic progenitor cell proliferation and alleviating symptoms associated in individuals diagnosed with or thought to have Essential Thrombocythemia (ET). Also provided herein are methods for using telomerase inhibitors for maintaining blood platelet counts at relatively normal ranges in the blood of individuals diagnosed with or suspected of having ET.

Abstract: Orthogonally protected 3?-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3?-amino group in the presence of the unprotected nucleoside base.

Abstract: Provided herein are antisense oligonucleotides that can effectively prevent or decrease c-myc protein expression as well as decrease overall rates of cell proliferation in in vitro and mammalian in vivo models of cell proliferative disorders as well as methods for using the same.

Abstract: Provided herein are methods for identifying individuals diagnosed with a cell proliferative disorder that will benefit from treatment with a telomerase inhibitor compound. Also provided herein are methods for treating these individuals with telomerase inhibitor compounds.

Abstract: A method and kit for inhibiting the proliferation of carcinoma cells are disclosed, based on a combination of an EGF pathway inhibitor and a telomerase inhibitor. When used in cancer therapy, the two compounds in combination enhance the anti-cancer treatment efficacy obtained with the antibody alone or the telomerase inhibitor alone.

Abstract: The present disclosure relates to RNA amidates and thioamidates useful for RNA interference applications. The RNA amidates and thioamidates contain at least one internucleoside linkage chosen from ribo-N3??P5? phosphoramidate (NP) and ribo-N3??P5? thiophosphoramidate (NPS) linkages, and optionally further containing at least one covalently conjugated lipid moiety. Compositions comprising the amidates and thioamidates are disclosed, as are methods for their use in modulating gene expression.

Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Abstract: Oligonucleotide conjugates, where an oligonucleotide is covalently attached to an aromatic system, are provided. In particular embodiments the oligonucleotide is complementary to the RNA component of human telomerase and is covalently attached to a nucleobase via an optional linker. The conjugates inhibit telomerase enzyme activity.

Abstract: Orthogonally protected 3?-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3?-amino group in the presence of the unprotected nucleoside base.