Abstract: The present invention provides a supplement and a culture media useful for culturing mammalian gametes and embryonic tissue. The culture media comprises at least one of recombinant human albumin, fermented hyaluronan, and citrate. Because the constituents are produced from non-conventional sources, the culture medium is free from contaminants such as viruses, prions and endotoxins. Additionally, because the medium is completely defined, the medium is not subject to variations which can impair the development of mammalian cells and prevent meaningful comparisons of empirical studies.

Abstract: Isolated and purified peptides and variants thereof, useful to prevent or treat antibody-mediated diseases, or indications caused by an undesirable antibody response to a given antigen, are provided. Also provided are peptides and methods useful to prevent or treat indications associated with the use of viral vectors in gene replacement therapy. Further, a method to inhibit or prevent aberrant immune responses to exogenous, non-infectious antigen is provided.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease.

Abstract: A novel gene therapy for cancer has been discovered, which unlike most prior appraches, does not require specific knowledge of the cancer cells, but instead targets a general characteristic that distinguishes cancer cells from normal cells, i.e., elevated eIF4E expression. The expression of a toxin or conditional toxin such as HTK is translationally repressed in normal cells by placing a complex 5′ UTR in front of its reading frame. In prototype experiments, this HTK mRNA, a transcriptional product of the BK-UTK vector, was translationally regulated so as to largely inhibit its production in normal murine and human cells, while cancer cells efficiently translated the protein, which a resulting increased sensitivity to GCV. Synthesis of the HTK protein from the BK-UTK vector (containing the 5′ UTR of Fibroblast growth factor −2 (“FGF-2”) readily occurred in a panel of murine and human breast carcinoma lines, but not in normal cell lines.

Abstract: Targeted ligand-liposome-therapeutic molecule complexes (vectors) for the systemic delivery of the therapeutic molecule to various target cell types including cancer cells such as squamous cell carcinoma of the head and neck, breast and prostate tumors. The preferred ligands, folate and transferrin, target the liposome complex and facilitate transient gene transfection. The systemic delivery of complexes containing DNA encoding wild-type p53 to established mouse xenografts markedly sensitized the tumors to radiotherapy and chemotherapy. The combination of systemic p53 gene therapy and conventional radiotherapy or chemotherapy resulted in total tumor regression and long tern inhibition of recurrence. This cell-specific delivery system was also used in vivo to successfully deliver, via intravenous administration, small DNA molecules (oligonucleotides) resulting in chemosensitivity and xenograft growth inhibition.

Abstract: The present invention comprises novel preparations of polyoxypropylene/polyoxyethylene copolymers which retain the therapeutic activity of the commercial preparations, but are substantially free from the undesirable effects which are inherent in the prior art preparations. Because the preparations of polyoxypropylene/polyoxyethylene copolymers which comprise the present invention are a less polydisperse population of molecules than the prior art polyoxypropylene/polyoxyethylene copolymers, the biological activity of the copolymers is better defined and more predictable.

Abstract: A method of making a microparticle that contains DNA coding for a polypeptide is described in which a solvent extraction method is used and solvent extraction takes place at elevated temperature. Oral administration of the microparticle leads to its expression. DNA coding for an immunogen is for stimulating antibody formation in a recipient and DNA coding for a non-immunogenic polypeptide is for gene therapy applications. DNA is incorporated into the microparticle without destruction of its function.

Abstract: Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within genes encoding for therapeutic antigens to produce altered polypeptides with enhanced antigenic and immunogenic activity. Moreover, these methods are useful for generating effective vaccines.

Abstract: This invention relates to an isolated DNA molecule encoding a Sox-9 gene which codes for the Sox-9 polypeptide. The human SOX-9 gene has been mapped to chromosome 17 in the same region as CMPD-1, the locus for Campomelic Dysplasia (CD). Sox-9 appears to have a role in mammalian skeletal development, and is used in the treatment of diseases involving bone or cartilage deficiency.

Abstract: Cationic cytofectins and liposomes comprising the same are disclosed which are especially useful for delivering exogenous compounds into cells in vitro and in vivo. The liposomes may comprise (a) a neutral lipid such as dioleoylphosphatidyl-ethanolamine (DOPE) or similar lipid-like compounds such as 1,2-dioleoyl-oxiphosphatidylethanolamine or other lipid-like structures and (b) one or more of the cationic cytofectins provided herein. The invention provides transfection kits and methods for delivery of exogenous compounds into cells.

Abstract: The present invention provides a gene-targeted, non-human mammal having a gene encoding a mutant protein product of a mutated FAD presenilin-1 (PS-1) gene, a human FAD Swedish mutation, and a humanized A&bgr; mutation, and generational offspring thereof and a gene-targeted, non-human mammal having a gene encoding a mutant protein product of a mutated FAD PS-1 gene and a human Swedish APP695 mutation, and generational offspring thereof, as well as methods of identifying compounds useful in treating Alzheimer's disease, and to methods of treating Alzheimer's disease.

Abstract: The present invention relates to lipid-based formulations for nucleic acid delivery to cells, methods for the preparation of such formulations and, in particular, to lipid encapsulated plasmids. The compositions are safe and practical for clinical use. In addition, the present invention provides methods for introducing nucleic acids into cells and for inhibiting tumor growth in cells using such lipid-nucleic acid formulations.

Abstract: This invention relates to stable non-aqueous formulations which are suspensions of proteinaceous substances or nucleic acids in non-aqueous, anhydrous, aprotic, hydrophobic, non-polar vehicles with low reactivity. More specifically, the present invention relates to stable protein or nucleic acid formulations wherein the compound remains in stable, dry powder form, yet the formulation is flowable and, therefore amenable to delivery to an animal via injection, transdermal administration, oral delivery or using an implantable device for sustained delivery. These stable formulations may be stored at elevated temperatures (e.g., 37° C.) for long periods of time and are especially useful as flowable formulations which can be shipped and/or stored at high temperatures or in implantable delivery devices for long term delivery (e.g., 1-12 months or longer) of drug.

Abstract: It provides a gene-entrapping liposome preparation which can be preserved over a long period of time, and a process for the preparation of the same. The preparation can be prepared by adding an aqueous solution of disaccharide to gene-entrapping liposomes. The frozen preparation can be preserved for 6 months or more at preservation temperature of −20° C., and the preparation shows excellent restoration ability in water and does not show reduction in biological activity. In the case of the lyophilized preparation, it can be preserved for longer time of about 1 year, shows excellent restoration ability in water, and does not show reduction in biological activity.

Abstract: Described is the use of lithium (Li+) for the preparation of a therapeutic composition for the introduction of a polynucleotide into a cell.

Abstract: The instant invention discloses compositions and methods related to epsin 3, a novel protein closely related to, but distinct from previously described epsins. Epsin 3 mRNA and protein are undetectable in keratinocytes isolated from unwounded skin, but is induced in cells following contact with fibrillar type I collagen. It is envisioned that this protein plays an important role in activated epithelial cells during tissue morphogenesis.

Abstract: The present invention relates to a novel method of genetic modification, wherein a nucleic acid of interest is transferred across a biological membrane, and/or directed to a specific location within or on a cell, by use of a synthetic transport entity. The transport entity according to the invention is new as such and produced by coupling a functional element (FE), such as a nuclear localization signal (NLS), an antennapedia peptide of a protein comprising both membrane translocation and nuclear transport properties, to a binding element (BE), such as a peptide nucleic acid (PNA), preferably separated by a linker molecule, which combination is then hybridized to a BE target sequence present on a carrier, which also includes the nucleic acid of interest. The present nucleic acid of interest may for example be a gene encoding a peptide, a protein or an RNA, or any other nucleic acid useful in genetic recombination events.

Abstract: Nucleic acid sequences encoding splice variants of BRCA1 are provided.

Abstract: The present invention is directed to a novel strain of feline immunodeficiency virus, designated herein as FIV-141, and to attenuated forms of the virus produced by mutating specific regions of the viral genome. The virus and mutated forms of the virus may be used to induce the production of antibodies to FIV-141, and in vaccines designed to protect cats from FIV.

Abstract: Novel methods of treating subjects afflicted with an androgen-dependent disorder, such as prostate cancer and benign prostatic hyperplasia are disclosed. Specifically, methods of treating androgen-dependent disorders by introducing a polypeptide or a polynucleotide encoding the polypeptide, which enhances inactivation of active androgens, are described.