Abstract: This application relates to iRNA agents and methods of making and using the agents. The iRNA agent comprises a sense sequence and an antisense sequence. The antisense strand and/or the sense strand may contain formula (8) or its L-nucleoside or 2?-5? linkage isomer: The iRNA agents of the invention can present increased nuclease resistance.

Abstract: A method of treating a tumor or a viral disease by administering to a human the following 2?,5?-oligoadenylate analog: Wherein m is 0; n is 0 or 1; R1 is alkoxy substituted by hydroxyl, mercapto, alkylthio substituted by hydroxyl or X1—X2—X3—S—; R2, R3, R4, R5 and R6 are hydroxyl, mercapto, alkylthio substituted by hydroxyl or X1—X2—X3—S—; R7 is oxygen, sulfur, —NH—, or —O(CH2CH2O)q-, wherein q is 2 to 6, or oxyalkyleneoxy; R8 is hydrogen or a 5?-phosphorylated oligonucleotide which has one hydroxyl removed from the 5?-phosphoric acid; E1 is K2; E2 is K1; E3 is K2 or K3 and E4 is K1, K2 or K3; K1 is K2 is K3 is B is adeninyl; A is alkylene; D is alkyl or alkenyl; X1 is alkyl or phenyl; X2 is —C(?O)O—, —OC(?O)— or —C(?O)S—; and X3 is alkylene.

Abstract: The present invention provides a regeneration promoter for regenerating tissue with the use of somatic stem cells. The invention also provides a cell fusion promoter comprising ATP or its metabolite which is safely usable in vivo, a method of producing fused cells in the presence of ATP or its metabolite and a related pharmaceutical composition for regenerating or improving the function of a tissue or an organ in a subject suffering from dysfunction or hypofunction due to injury or denaturation.

Abstract: An improved understanding and method for the clinical adjuvant and immunomodulatory use of dsRNAs and ply-ICLC in particular, alone or in conjunction with other drugs and various vaccines designed to prevent or treat various microbial, viral, neoplastic, autoimmune diseases, and or degenerative diseases.

Abstract: A 2-5A analog represented by the formula (1): wherein m is 0 or 1; n is 0 to 2; R1 represents an alkoxy group having from 1 to 6 carbon atoms which may be substituted, an unprotected mercapto group, a mercapto group protected by a nucleic acid synthesis protecting group, or an alkylthio group having from 1 to 4 carbon atoms which may be substituted; R2, R3, R4, R5 and R6 represent an unprotected hydroxyl group, a hydroxyl group protected by a nucleic acid synthesis protecting group, an alkoxy group having from 1 to 6 carbon atoms which may be substituted, an unprotected mercapto group, a mercapto group protected by a nucleic acid synthesis protecting group, or an alkylthio group having from 1 to 4 carbon atoms which may be substituted; R7 represents an oxygen atom, or a —O(CH2CH2O)q- group, wherein q is 2 to 6; R8 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms which may be substituted, or a 5?-phosphorylated oligonucleotide analog which has one hydroxyl group removed from the 5

Abstract: The present invention relates to oligoribonucleotide derivatives which have a 2?5?-linked oligoribonucleotide residue without a 5?-phosphate residue on the 3? end and to the use thereof for specific inhibition of gene expression.

Abstract: The invention provides methods for modulating the immune response caused by CpG-containing oligonucleotides. The methods according to the invention enable both decreasing the immunostimulatory effect for antisense applications, as well as increasing the immunostimulatory effect for immunotherapy applications.

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: The invention provides polyamide-oligonucleotide derivatives of the formula: F[(DNA-Li)q(PNA-Li)r(DNA-Li)s(PNA)t]xF?. In the formula, q, r, s, and t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s, and t is greater than or equal to 2; and x is 1 to 20. In the formula, DNA is a nucleic acid such as DNA or RNA or a known derivative thereof. Li is a covalent linkage between DNA and PNA, where the covalent linkage comprises a bond or an organic radical with at least one atom from the series consisting of C, N, O, or S. PNA is a polyamide structure which contains at least one nucleotide base that is different from thymine. F and F? are end groups and/or are linked together by a covalent bond. The invention also provides physiologically tolerated salts of the above formula. The invention further provides a process for preparation of the polyamide-oligonucleotide derivatives of the invention as well as their use as pharmaceuticals, as gene probes, and as primers.

Abstract: This invention relates to an analytical support containing a plurality of oligonucleotides fixed on this support, where each of the nucleotides is marked by a fluorescent compound that presents a variation of fluorescence on the hybridization of each marked oligonucleotide with at complementary oligonucleotide. This support makes it possible to carry out an analysis of biological targets by measuring the variation of fluorescence in order to determine the hybridization of the targets with the oligonucleotides of the support.

Abstract: A coprecipitant and a nucleic-acid extraction method using the coprecipitant are provided. The coprecipitant has affinity to the nucleic acids, no competitive inhibition to the reverse transcription and no inhibition to the PCR reaction in case of extracting a very small amount of nucleic acids by alcoholic precipitation using isopropyl alcohol or ethanol. Further, the coprecipitant can precipitate with the nucleic acids as a visible white or blue precipitate, thereby to suppress technical errors and enhance the extraction efficiency. A coprecipitant which acts in a process of extracting the nucleic acids by centrifugal separation from biological materials and/or test samples in the same manner as nucleic acids and has ability for precipitating as a visible white or blue precipitate when being separating and concentrating it by alcohol.

Abstract: Methods for enhancing the production of viral vaccines in animal cell culture are described. These methods rely on the manipulation of the cellular levels of certain interferon induced antiviral activities, in particular, cellular levels of double-stranded RNA (dsRNA) dependent kinase (PKR) and 2′-5′ oligoadenylate synthetase (2-5A synthetase). In cell cultures deficient for PKR or 2-5A synthetase, viral yield is enhanced by several orders of magnitude over cell cultures with normal levels of these proteins making these cell cultures useful for the production of viral vaccines.

Abstract: Methods for enhancing the production of viral vaccines in animal cell culture are described. These methods rely on the manipulation of the cellular levels of certain interferon induced antiviral activities, in particular, cellular levels of double-stranded RNA (dsRNA) dependent kinase (PKR) and 2′-5′ oligoadenylate synthetase (2-5A synthetase). In cell cultures deficient for PKR or 2-5A synthetase, viral yield is enhanced by several orders of magnitude over cell cultures with normal levels of these proteins making these cell cultures useful for the production of viral vaccines.

Abstract: The invention provides Defl polypeptides and DNA (RNA) encoding Defl polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing Defl polypeptides to screen for antibacterial compounds.

Abstract: The present invention relates to chimeric molecules comprising an oligonucleotide complementary to a region of the ribonucleotide component of telomerase attached to an activator of RNase L (“activator-antisense complex”) which specifically cleaves the ribonucleotide portion of a telomerase enzyme. The present invention relates to methods of inhibiting telomerase enzymatic activity with activator-antisense complexes targeted to the RNA component of telomerase. The present invention further relates to methods of treating malignant neoplastic disease, wherein the malignant cells contain a telomerase activity that is necessary for the growth of the malignant cells.

Abstract: The invention relates to novel modified oligonucleotides, the construction thereof, and their use in oligonucleotide-based therapies. More specifically, the invention is to novel oligonucleotides having modified internucleoside linkages which are resistant to nucleases, having enhanced ability to penetrate cells, and which are capable of binding target oligonucleotide sequences in vitro and in vivo. The modified oligonucleotides of the invention are particularly useful in oligonucleotide-based therapies utilizing the modified oligonucleotides to interrupt protein synthesis or transcription or to otherwise inactivate messenger RNA or double stranded DNA.

Abstract: The present invention relates to novel DNA sequences that encode for the branched-chain alpha-ketoacid dehydrogenase complex of an organism belonging to the genus Streptomyces and to novel polypeptides produced by the expression of such sequences. It also relates to novel methods of enhancing the production of natural avermectin, of producing a Streptomyces avermitilis bkd mutant and of producing novel avermectins through fermentation.

Abstract: The invention provides def1 polypeptides and polynucleotides encoding def1 polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing def1 polypeptides to screen for antibacterial compounds.

Abstract: Antiviral compounds have the formula wherein m is zero, 1, 2 or 3; n is from 1 to 8, preferably 1, 2 or 3; most preferably 1 or 2; R is independently selected from the group consisting of  provided that all R may not be R1 is independently selected from the group consisting of hydroxyl and hydrogen; R2 is independently selected from the group consisting of oxygen and sulfur; or water soluble salts thereof.

Abstract: Chimeric molecules comprising a virus targeting antisense oligonucleotide moiety attached to an activator of 2-5A-dependent RNase.

Abstract: The present invention relates to chimeric molecules comprising an oligonucleotide complementary to a region of the ribonucleotide component of telomerase attached to an activator of RNase L (“activator-antisense complex”) which specifically cleaves the ribonucleotide portion of a telomerase enzyme. The present invention relates to methods of inhibiting telomerase enzymatic activity with activator-antisense complexes targeted to the RNA component of telomerase. The present invention further relates to methods of treating malignant neoplastic disease, wherein the malignant cells contain a telomerase activity that is necessary for the growth of the malignant cells.

Abstract: The present invention provides a method of treating bacterial respiratory infections by pulmonary administration of protonated/acidified nucleic acids. These modified nucleic acids are effective as bactericidal and/or bacteriostatic agents without regard to the class of bacteria, so are especially useful when diagnosis is difficult or when multiple infectious organisms are present. The antibiotic activity of nucleic acids of the invention is not dependent on either the specific sequence of the nucleic acid or the length of the nucleic acid molecule.