Abstract: Disclosed is a delivery system for biologically active molecules or agents which must enter cells to exert their effect. The delivery system comprises a mixture of cationic lipid in combination with a receptor ligand and is particularly suited for intracellular delivery of polynucleotides.

Abstract: A virion expression system for a desired protein packaged in an envelope derived from a retrovirus useful in administering proteins which cross cell membranes in order to serve their function. Preferred virions are those that carry an RNA sequence that encodes cytokines or lymphokines, and includes IL-2, multiple drug resistance protein, and TNF.

Abstract: A new gene--MN--and proteins/polypeptides encoded therefrom are disclosed. Recombinant nucleic acid molecules for expressing MN proteins/polypeptides and recombinant proteins are provided. Expression of the MN gene is disclosed as being associated with tumorigenicity, and the invention concerns methods and compositions for detecting and/or quantitating MN antigen and/or MN-specific antibodies in vertebrate samples that are diagnostic/prognostic for neoplastic and pre-neoplastic disease. Test kits embodying the immunoassays of this invention are provided. MN-specific antibodies are disclosed that can be used diagnostically/prognostically, therapeutically, for imaging, and/or for affinity purification of MN proteins/polypeptides. Also provided are nucleic acid probes for the MN gene as well as test kits comprising said probes.

Abstract: The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

Abstract: The invention concerns new cationic or polycationic amphiphiles which are capable of forming aggregates with macromolecules, in particular with DNA or RNA, and it concerns their delivery into prokaryotic or eukaryotic cells. Compounds with spermyl-dioleoyloxypropyl structure have proven to be particularly preferable.

Abstract: The invention provides a human prostate-specific transcriptional regulatory sequence, polynucleotide comprising such regulatory regions, toxin gene constructs wherein a toxin gene is expressed under the transcriptional control of a human prostate-specific transcriptional regulatory sequence, and methods for treating prostate disease using such toxin gene constructs.

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: Nucleic acid fragments are described which can be used as probes for detecting one of the strands of the DNA tandem repeat sequence in the gene encoding the core protein of human polymorphic epithelial mucin, or incorporated into an expression vector to encode a portion of the mucin core protein to be used for immunization purposes.

Abstract: JNK-interacting protein 1 (JIP-1), an inhibitor of the JNK1 protein, and methods of treating a pathological condition or of preventing the occurrence of a pathological condition in a patient by the administration of a therapeutically effective amount of JIP-1 polypeptides, peptides, peptide mimetics, or nucleic acids are described.

Abstract: Compositions and methods for administering nucleic acid compositions in vitro to cells in culture or in vivo to an organism whereby the uptake of nucleic acids is enhanced are provided. Various compositions, including thermo-reversible gels, are utilized to increase the viscosity of an administered nucleic acid formulation, thereby prolonging the localized bioavailability of the administered nucleic acid.

Abstract: The present invention provides nucleic acid and corresponding amino acid sequences of a multifunctional protein that has been found to be useful in numerous medical and cosmetic contexts. A protein having "multifunctional activity," is defined herein as including at least one of a chymotrypsin, trypsin, collagenase, elastase or exo peptidase activity or asialo GM.sub.1 ceramide binding activity. These proteins are useful for multiple purposes, including treating viral infections such as herpes outbreaks, fungal, bacterial or parasitic infections, including the primary and secondary infections of leprosy, colitis, ulcers, hemorrhoids, corneal scarring, dental plaque, acne, cystic fibrosis, blood clots, wounds, immune disorders including autoimmune disease and cancer.

Abstract: Preparations of conjugates of a receptor-binding internalized ligand and a cytocide-encoding agent and compositions containing such preparations are provided. The conjugates contain a polypeptide that is reactive with an FGF receptor, such as bFGF, or another heparin-binding growth factor, cytokine, or growth factor coupled to a nucleic acid binding domain. One or more linkers may be used in the conjugation. The linker is selected to increase the specificity, toxicity, solubility, serum stability, or intracellular availability, and promote nucleic acid condensation of the targeted moiety. The conjugates are complexed with a cytocide-encoding agent, such as DNA encoding saporin. Conjugates of a receptor-binding internalized ligand to a nucleic acid molecule are also provided.

Abstract: A method to increase the efficiency of transduction of hematopoietic and other cells by retroviruses includes infecting the cells in the presence of fibronectin or fibronectin fragments. The fibronectin and fibronectin fragments significantly enhance retroviral-mediated gene transfer into the cells, particularly hematopoietic cells including committed progenitors and primitive hematopoietic stem cells. The invention also provides improved methods for somatic gene therapy capitalizing on enhanced gene transfer, hematopoietic cellular populations, and novel constructs for enhancing retroviral-mediated DNA transfer into cells and their use.

Abstract: The present invention relates to regulation and control of cellular processes by SH3-domain binding proteins, by putative signalling domains of such proteins, ligands of the signalling domain, and diagnosis and therapy based on the activity of such proteins, signalling domains, and ligands.

Abstract: The invention provides improved methods and products based on adenoviral materials which can advantageously be used in for instance gene therapy. In one aspect an adenoviral vector is provided which has no overlap with a suitable packaging cell line which is another aspect of invention. This combination excludes the possibility of homologous recombination, thereby excluding the possibility of the formation of replication competent adenovirus. In another aspect an adenovirus based helper construct which by its size is incapable of being encapsidated. This helper virus can be transferred into any suitable host cell making it a packaging cell. Further a number of useful mutations to adenoviral based materials and combinations of such mutations are disclosed, which all have in common the safety of the methods and the products, in particular avoiding the production of replication competent adenovirus and/or interference with the immune system. Further a method of intracellular amplification is provided.

Abstract: This invention provides a double-stranded oligonucleotide or a derivative thereof which comprises 15 to 40 base pairs, wherein at least one side of the strands contains at least one nucleotide sequence represented by 5'-TTTSSCGS-3' (S is G or C). Also, since the compound of the present invention can inhibit expression of growth-related genes which are regulated by E2F, through its function to undergo sequence-specific competitive inhibition of the binding of E2F protein to the transcription region at a low concentration, a pharmaceutical composition containing the inventive compound as its active ingredient is useful as a drug having low side effects for use in the prevention and treatment of cancers.

Abstract: Molecular complexes for targeting oligonucleotides, such as antisense oligonucleotides or ribozymes, to a specific cell to block expression of a gene or genes in the cell are described. The single-stranded poly- or oligonucleotide is complexed to a conjugate of a cell-specific binding agent and a poly- or oligonucleotide-binding agent. The cell-specific binding agent is specific for a cellular surface structure which mediates internalization of the complex. An example is the asialoglycoprotein receptor of hepatocytes. The poly- or oligodeoxy-nucleotide-binding agent is a compound such as a polycationic protein which stably complexes the oligonucleotide under extracellular conditions and releases it under intracellular conditions so that it can hybridize with the target RNA.

Abstract: Improved recombinant retrotransposon vectors for gene transfer are disclosed. The synthetic vectors are truncated so as to reduce or altogether eliminate homologous recombination with retroviral helper sequences found in helper cells used to propagate the vectors, making them safer for use in humans and providing more space for therpeutic genes. The vectors transmit foreign DNA efficiently, are stable, enable abundant RNA expression from the retrotransposon transcriptional promoter, and through their diversity permit many useful applications in therapeutics and transgenics. Methods are described for rescuing tissue-specific spromoters obtaining expression in primary cells, mapping the genome and other techniques of therapeutic and transgenic utility.

Abstract: The invention provides a two component system for use in association with one another comprising:(a) a vector capable of expressing an enzyme at the surface of a cell; and(b) a prodrug which can be converted into an active drug by said enzyme, useful in the treatment of tumours.

Abstract: The present invention relates to regulation and control of cellular processes by SH3-domain binding proteins, by putative signalling domains of such proteins, ligands of the signalling domain, and diagnosis and therapy based on the activity of such proteins, signalling domains, and ligands.