Abstract: A process for the synthesis of phosphorothioate oligonucleotides is provided which comprises assembling an oligonucleotide bound to a solid support in the presence of acetonitrile; prior to cleaving the oligonucleotide from the solid support removing the acetonitrile; and cleaving the oligonucleotide from the solid support. The process is particularly suited to the large scale synthesis of nucleotides.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, such as breast cancer, are disclosed. Compositions may comprise one or more breast tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a breast tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as breast cancer. Diagnostic methods based on detecting a breast tumor protein, or mRNA encoding such a protein, in a sample are also provided.

Abstract: A compound capable of acting as a cationic lipid is described. The compound comprises a cholesterol group having linked thereto a head group; wherein the head group is more positive than the head group of DC-Chol.

Abstract: Experimental and analytical methods enable reconstruction of signal transduction networks from gene expression profiles. Signal transduction pathways can be reverse-engineered by 1) experimentally manipulating individual genes, 2) generating cellular expression profiles, and 3) analyzing for common patterns among these profiles. Analysis of patterns among profiles permits reconstruction of pathways and networks of interrelationships among genes and their products.

Abstract: The present invention relates to compositions and methods which enhance the local and systemic uptake and delivery of oligonucleotides and nucleic acids via non-parenteral routes of administration. Pharmaceutical compositions comprising oligonucleotides disclosed herein include, for systemic delivery, emulsion and microemulsion formulations for a variety of applications and oral dosage formulations. It has also surprisingly been discovered that oligonucleotides may be locally delivered to colonic sites by rectal enemas and suppositories in simple solutions, e.g., neat or in saline. Such pharmaceutical compositions of oligonucleotides may further include one or more penetration enhancers for the transport of oligonucleotides and other nucleic acids across mucosal membranes.

Abstract: The invention concerns novel compounds of formula (I) in which: R1 and R2, which are identical or different, are C6-C23 alkyl or alkenyl radicals, linear or branched or —C(═O)—(C6-C23) alkyl or -c(═O)—(C6-C23) alkenyl, linear or branched. X is the oxygen atom or an amino-NR3 radical, R3 being a hydrogen atom or an inferior alkyl radical of 1 to 4 carbon atoms; n is a positive whole number from 1 to 6; m is a positive whole number from 1 to 6, and when n>1, m can be identical or different. The invention also concerns novel compositions of said compounds and of active substances in particular therapeutically, comprising at least a negative charge for inserting said active susbtances in cells. It concerns in particular novel complexes, of which the active substance consists of one or several nucleic acids, useful for cell transfection.

Abstract: A synthetic nuclease resistant antisense oligodeoxynucleotide capable of selectively modulating expression of human tumor necrosis factor-alpha by targeting exon sequences flanking donor splice sites, thereby regulating expression of TNF-&agr; in a patient in need of such therapy is provided. In an embodiment either AS—ODN having the sequence set forth in SEQ ID No:4 or SEQ ID No:6 or a combination thereof can be used. The AS—ODN is administered either as the active ingredient in a pharmaceutical composition or by utilizing gene therapy techniques as an expression vector.

Abstract: The invention involves methods and materials for extracellularly administering PNA oligomers to living cells. Specifically, the invention provides methods and materials of treating living cells with PNA oligomers such that the oligomers cross biological barriers and engender a biological response in a sequence specific manner. In addition, the invention provides methods and materials for orally administering PNA oligomers to animals such that the oligomers cross biological barriers and engender a biological response in a sequence specific manner. The invention also provides sense and antisense PNA oligomers that modulate transcription and translation, respectively. The invention also provides mismatch PNA oligomers that modulate the degree of an engendered biological response. In addition, the invention provides methods and materials for detecting PNA oligomers within a biological sample collected from an animal.

Abstract: A novel growth factor, persephin, which belongs to the GDNF/neurturin family of growth factors, is disclosed. The human, mouse and rat amino acid sequences have been identified. Human, mouse and rat persephin genomic DNA sequences have been cloned and sequenced and the respective cDNA sequences identified. In addition, methods for treating degenerative conditions using persephin, methods for detecting persephin gene alterations and methods for detecting and monitoring patient levels of persephin are provided. Methods for identifying additional members of the persephin-neurturin-GDNF family of growth factors are also provided.

Abstract: Peptide nucleic acids conjugated to lipophilic groups and incorporated into liposomes exhibit enhanced cellular uptake and distribution. Cellular uptake and distribution of peptide nucleic acids also increases with the introduction of an amino acid side chain into the backbone of peptide nucleic acids. Methods of modulating cellular uptake and methods for treating animals are provided. The peptide nucleic acids of the invention comprise naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone.

Abstract: A method is described for improving the pharmacokinetics of a drug in a subject, by co-administering oligomers, preferably PMO's (phosphorodiamidate morpholino oligonucleotides), antisense to RNAs encoding drug-metabolizing enzymes, particularly p450 enzymes. The oligomers reduce production of the drug-metabolizing enzymes, which extends drug half-life and effectiveness and/or decreases drug toxicity.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, particularly breast cancer, are disclosed. Illustrative compositions comprise one or more breast tumor polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly breast cancer.

Abstract: A method is described for improving the pharmacokinetics of a drug in a subject, by co-administering oligomers, preferably PMO's (phosphorodiamidate morpholino oligonucleotides), antisense to RNAs encoding drug-metabolizing enzymes, particularly p450 enzymes. The oligomers reduce production of the drug-metabolizing enzymes, which extends drug half-life and effectiveness and/or decreases drug toxicity.

Abstract: The invention relates to an oligonucleotide derivative which comprises at least one nucleoside building block of the formula (I) The invention furthermore relates to nucleoside building blocks, intermediates and processes for preparing the oligonucleotide derivatives and the nucleoside building blocks. The invention also relates to pharmaceutical compositions and to uses of the oligonucleotide derivatives and the nucleoside building blocks.

Abstract: Methods for identifying organisms capable of degrading fumonisin. Fumonisin can be incorporated into culture medium for selection of organisms resistant to fumonisin and/or capable of growing on fumonisin as a sole carbon source. Using this method, several organisms have been identified. These organisms can be used to isolate the enzymes and the genes responsible for conferring fumonisin-resistance. The gene can be cloned and inserted into a suitable expression vector so that the protein can be further characterized. Additionally, the DNA encoding for fumonisin degrading enzymes can be used to transform plant cells normally susceptible to Fusarium or other toxin-producing fungus infection. Plants can be regenerated from the transformed plant cells. In this way, a transgenic plant can be produced with the capability of degrading fumonisin, as well as with the capability of producing the degrading enzymes.

Abstract: The present invention relates to nucleic acid molecules with new motifs having catalytic activity, methods of syntheses and uses thereof.

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

Abstract: A method is disclosed for identifying and producing L-nucleic acids which interact with a target molecule having a natural configuration, as well as the L-nucleic acids produced by this method. Also disclosed is the use of D-nucleic acids which bind to the optical antipode of the target molecule as a matrix for producing L-nucleic acids with an identical sequence, and pharmaceutical compositions and kits which contain the disclosed L-nucleic acids.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, such as breast cancer, are disclosed. Compositions may comprise one or more breast tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a breast tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as breast cancer. Diagnostic methods based on detecting a breast tumor protein, or mRNA encoding such a protein, in a sample are also provided.

Abstract: Novel lipid-nucleic acid particulate complexes which are useful for in vitro or in vivo gene transfer are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. Upon removal of a solubilizing component (i.e., detergent or an organic solvent) the lipid-nucleic acid complexes form particles wherein the nucleic acid is serum-stable and is protected from degradation. The particles thus formed have access to extravascular sites and target cell populations and are suitable for the therapeutic delivery of nucleic acids.