Abstract: Cell-based gene transfer is effected by administering transfected cells containing an expressible transgene into the pulmonary system of a patient, where the cells express and secrete expression products of the transgene directly into the pulmonary system. Also provided is the use of angiogenic factors in treatment of pulmonary hypertension.

Abstract: The invention relates to methods for treatment of neurological disease by administering an agent which interacts with a retinoid receptor associated with the neurological disease. The invention is also related to a method of modulating dopamine receptor synthesis by introducing an agent that interacts with a retinoid receptor associated with the dopamine receptor synthesis. The invention is further related to a transgenic animal, e.g., mouse, and mammalian cell line, which is deficient in the normal synthesis of one or more receptors of RAR&agr;, &bgr;, &ggr; and RXR, and cell line thereof.

Abstract: The invention is directed to a method of in vivo selection for genetically modified hematopoietic progenitor cells from nonmodified hematopoietic cells in a subject. Ibis goal is accomplished by introducing mutant dihydrofolate reductase genes into hematopoietic progenitor cells and then administering to a subject harboring the resultant transformed cells an antifolate and a nucleoside transport inhibitor. The invention is also directed to nucleic acids encoding mutant dihydrofolate reductase genes and to hematopoietic cells transformed with such mutant genes.

Abstract: Novel parathyroid hormone peptide (PTH) and parathyroid hormone related peptide (PTHrP) or derivatives thereof which are biologically active are disclosed, as are pharmaceutical compositions containing said peptides, and synthetic and recombinant methods for producing said peptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing said peptides. Also disclosed are methods for screening candidate compounds of the invention for antagonistic or agonistic effects on parathyroid hormone receptor action. Also disclosed are diagnostic and therapeutic methods of said compounds.

Abstract: The invention relates to a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; (b) expressing the genetic elements to produce their respective gene products within the microcapsules; (c) sorting the genetic elements which produce the gene product having a desired activity. The invention permits the in vitro evolution of nucleic acids by repeated mutagenesis and iterative applications of the method of the invention.

Abstract: Cell-based gene transfer is effected by administering transfected cells containing an expressible transgene coding for an angiogenic factor or other therapeutic factor, into the pulmonary circulation of a patient, where the cells express and secrete expression products of the transgene to act locally at the site of expression of expression, and in some cases to be conveyed by the patient's circulation to other body organs. The process is especially useful in treatment of pulmonary hypertension by means of expressed angiogenic factors. Also provided is the use of angiogenic factors, delivered by other means than cell-based gene transfer, in treating pulmonary hypertension.

Abstract: Construct-complexes of a hemoglobin, a hepatocyte modifying substance bound to the hemoglobin, and a haptoglobin bound to the hemoglobin, are provided, for administration to mammalian patients. The construct-complex may be formed ex vivo, or a hemoglobin-hepatocyte modifying substance combination may be administered to the patient so that haptoglobin in the mammalian body bonds thereto to form the construct-complex in vivo. Disorders of the liver may be diagnosed and treated using construct-complexes described herein.

Abstract: Described are recombinant adenoviral vectors retaining sufficient E4 sequences to improve the expression and/or persistence of expression of a gene of interest. Furthermore, the invention describes the use of a polynucleotide encoding one or more ORF(s) of the E4 region of an adenovirus selected from ORF1, ORF2, ORF3, ORF4, ORF3/4, ORF6/7, ORF6 and ORF7 taken individually or in combination, to improve the expression and/or persistence of expression of a gene of interest operably linked to regulatory elements and inserted into an expression vector. Finally, a host cell, a composition, an infectious viral particle comprising such a polynucleotide or adenoviral vector, a method for preparing said viral particle as well as their therapeutic use are described.

Abstract: The invention concerns composititions and methods for the diagnosis and treatment of neoplastic cell growth and proliferation in mammals, including humans. The invention is based on the identification of cardiotrophin-1 gene amplified in the genome of tumor cells. Such gene amplification is expected to be associated with the overexpression of the gene product and contribute to tumorigenesis. Accordingly, the cardiotrophin-1 polypeptide encoded by the amplified gene is believed to be a useful target for the diagnosis and/or treatment (including prevention) of certain cancers, and may act as a predictor of the prognosis of tumor treatment.

Abstract: The present invention provides a universal immunomodulatory cytokine-expressing bystander cell line, a composition comprising such a cell line cancer antigen, a method of making such a cell line, and a method of using such a composition.

Abstract: A gene therapy system is disclosed that selectively kills leukemia cells in bone marrow, while leaving stem cells unaffected. All cells in a mixture of stem cells and leukemia cells are transfected with a high efficiency gene transfer vector. The vector carries a eukaryotic expression construct encoding a toxin gene. This toxin gene is expressed only in leukemia cells, not in stem cells. Differential expression of the toxin gene in leukemia cells and stem cells may be achieved by placing the coding sequence under the control of an appropriate promoter, such as the RSV promoter or the SV40 promoter. High gene expression has been demonstrated in a panel of transformed leukemia cell lines, but no gene expression in transformed, CD34-selected, primary human stem cells. The treatment will be useful not only for leukemia patients, but also for other cancer patients undergoing autologous bone marrow transplants (e.g., breast or lymphoma cancers).

Abstract: Several genes encoding subunits of the neuronal nicotinic acetylcholine receptors have been cloned and regulatory elements involved in the transcription of the &agr;:2 and &agr;:7 subunit genes have been described. Yet, the detailed mechanisms governing the neuron-specific transcription and the spatio-temporal expression pattern of these genes remain largely uninvestigated. The &bgr;2-subunit is the most widely expressed neuronal nicotinic receptor subunit in the nervous system. We have studied the structural and regulatory properties of the 5′ sequence of this gene. A fragment of 1163 bp of upstream sequence is sufficient to drive the cell-specific transcription of a reporter gene in both transient transfection assays and in transgenic mice. Deletion analysis and site-directed mutagenesis of this promoter reveal two negative elements and one positive element. The positively acting sequence includes one functional E-box.

Abstract: This invention includes retrovirus envelope mutants into which heterologous peptide or glycopeptide sequences can be linked for expression and stable presentation on retroviral vectors. The envelope mutants are characterized by the ability to restore the target penetration capability that is lost or greatly diminished upon fusion of heterologous sequences to the wild type envelope protein and the ability to increase the fusion envelope protein stability and decrease envelope shedding from virus particles. The envelope mutants are created by rotating residues in at least one of 7 motifs. The disclosed envelope proteins also can be used in liposome or pseudotype-virus compositions for delivery of agents including nucleic acid molecules. Methods of preparing and utilizing these envelope mutants in gene therapy are also described.

Abstract: The present invention provides polypeptides comprising an immunogenic epitope of a M. vaccae protein, polynucleotides encoding such polypeptides, and fusion proteins comprising at least one such polypeptide, together with DNA constructs comprising at least one inventive polynucleotide. Compositions comprising such polypeptides, polynucleotides, fusion proteins and/or DNA constructs may be employed in the treatment of infectious diseases and immune disorders.

Abstract: The subject of the present invention is the use of a polypeptide comprising at least 6 continuous amino acids of the sequence as shown in the sequence identifiers 1 to 5 as cellular receptor and/or coreceptor for adenoviruses. It also relates to the use of a cell capable of expressing such a polypeptide as well as that of a ligand capable of influencing the attachment of an adenovirus to a host cell and/or its entry into the said host cell. Finally, it also relates to a method for selecting or identifying a cellular receptor for a virus or the part of a viral protein which determines the attachment of the virus to its cellular receptor as well as to the use of a bifunctional ligand to target an adenovirus to a host cell carrying, at its surface, a surface protein other than the natural cellular receptor for the said adenovirus.

Abstract: Disclosed herein are novel medical devices, particular well-suited for sustained delivery of therapeutically-significant substances. Also disclosed are methods of making and using these delivery devices. Using these devices and methods, the present invention teaches sustained, targeted and reversible delivery of immunostimulating agents, as well as therapeutic agents such as enzymes, hormones and neurotransmitters, to name but a few.

Abstract: A recombinant replication competent retrovirus for gene deliver and gene therapy is provided. The recombinant retrovirus has a heterologous nucleic acid sequence, a sequence encoding a cell- or tissue-specific ligand or a sequence for transcriptional targeting, or a combination of both a cell- or tissue-specific ligand and a cell- or tissue-specific transcriptional targeting sequence.

Abstract: The infectious clone comprises: a) a complete copy of the complementary DNA (cDNA) to the genomic RNA of the turnip mosaic virus (TuMV), in the form of double stranded DNA, b) a transcription promoter sequence, c) a replicon and, optionally, d) a transcription termination or polyadenilation sequence. Viral vectors comprise an infectious clone modified to contain a gene or a heterologous gene fragment. Infectious viral clones and vectors are useful for basic research, in virology and for the expression of genes and epitopes of interest.

Abstract: Human mesenchymal stem cells having the phenotype SH3+, CD45+ can be isolated. These precursor mesenchymal item cells are useful for treatment of patients in need of mensenchymal stem cell.

Abstract: The methods of the present invention are based on the discovery that adverse side effects (such as hemorrhage) can occur upon infusion of cells that express tissue factor. Accordingly, the methods of the invention are aimed at reducing the biological activity of tissue factor (TF) in a patient, and can be carried out by, for example: infusing fewer cells (or infuse the same number of BMSCs over a longer period of time); reducing the expression or activity of TF (within the infused cells specifically (e.g., by contacting the cells with a TF antagonist in vitro) or within the patient generally (e.g., by administering a TF antagonist to the patient); hampering the interaction of TF with factor VII(a); inhibiting the activity of the TF-factor VII(a) complex once it has formed; or inhibiting the coagulation cascade at any point downstream from formation of the complex (including inhibition of platelet activation).