Abstract: The present invention provides methods for inhibiting the growth of selected tumors utilizing recombinant viral vectors. Briefly, within one aspect of the present invention, a method for inhibiting the growth of a selected tumor is provided comprising the step of directly administering to a warm-blooded animal a vector construct which directs the expression of at least one anti-tumor agent, such that the growth of said tumor is inhibited. Representative examples of anti-tumor agents include immune activators and tumor proliferation inhibitors.

Abstract: The present invention concerns a retroviral vector for introducing into a eucaryotic cell DNA encoding a transcription unit which comprises a first DNA sequence which is the reverse transcript of at least a portion of a retrovirus, said portion including both the 5' LTR sequence and the 3' LTR sequence of the retrovirus, and a second DNA sequence encoding the transcription unit which is inserted into the U3 region of the 3' LTR sequence. A method of producing a virion useful for introducing into a eucaryotic cell DNA encoding a transcription unit is provided as well as a method of introducing into a eucaryotic cell DNA encoding a transcription unit which comprises infecting the cell with such a virion.

Abstract: A drug delivery virion which contains an expression system for the desired protein active ingredient packaged in an envelope derived from a retrovirus is especially useful in administering materials which need to cross cell membranes in order to serve their function.

Abstract: The present invention relates to the identification of novel nucleic acid molecules and proteins encoded by such nucleic acid molecules or degenerate variants thereof, that participate in the control of mammalian body weight. The nucleic acid molecules of the present invention represent the genes corresponding to the mammalian tub gene, a gene that is involved in the regulation of body weight.

Abstract: Whole cell or cell-free test systems for screening and identifying compounds that modulate or alter Cyclin E activity. Whole cell assays measure the G1 phase of cells in the presence or absence of the test compound. Additional whole cell or cell-free assays measure binding of cyclin E to a cell division kinase, measure cyclin E activity directly, or measure the cell division kinase activity directly in the presence or absence of the test compound.

Abstract: Modified retroviral vector particles and modified retroviral producer cells producing such particles are provided for facilitating gene therapy procedures involving the transduction of target cells with retroviral vector particles in the presence of complement containing body fluids. The modifications involve genetic alterations to effect the expression by these cells and particles of complement inhibitor activity. The genetic alterations involve the introduction of nucleic acid expression constructs directing the expression of retroviral SU(gp70)/complement inhibitor chimeric proteins into cells from which the producer cells are derived.

Abstract: The invention is a synthetic DNA sequence for encoding a specific enzyme or protease. The protease is essential for the completion (replication) of an infective human immunodeficiency virus (HIV). The invented gene is desirable for the expression of the protease by recombinant methodology in prokaryotic and/or eukaryotic cells and the production of a commercially desirable amount of the protease for biochemical and physical characterization, necessary to find effective inhibitor of the protease, and thereby to block the production of infectious human immunodeficiency virus (HIVs).

Abstract: A drug delivery virion which contains an expression system for the desired protein active ingredient packaged in an envelope derived from a retrovirus is especially useful in administering materials which need to cross cell membranes in order to serve their function.

Abstract: Recombinant avipox viral vectors which express heterologous polypeptides capable of assembling into defective nonself-propagating viral particles are disclosed. The recombinant avipox viruses can be used to produce significant amounts of the heterologous polypeptides in avian or non-avian cells. Preferably, the recombinant avipox virus is a fowlpox virus. The viral particles can also be used as immunogens and for targeted delivery of heterologous gene products and drugs.

Abstract: The present invention relates to a system comprising a modified bacterial gene for cytosine deaminase that has been engineered into a eukaryotic expression vector and the expression of the gene by mammalian cells.The present invention further relates to methods, gene therapies and vaccines that employ the negative selectable marker, cytosine deaminase, which has the ability to produce a toxic antimetabolic 5-fluorouracil from 5-fluorocytosine.

Abstract: Recombinant viral vectors which coexpress heterologous polypeptides capable of assembling into defective nonself-propagating viral particles are disclosed. The viral vectors as well as the viral particles can be used as immunogens and for targeted delivery of heterologous gene products and drugs.

Abstract: A process for culturing and generating a chimeric cell culture, in particular chimeric epithelium, is disclosed. The chimeric epithelium can be used to treat skin trauma such as burn victims. Autologous epithelial grafts have been used on burn patients although this requires that the patient's cells are cultured and expanded in vitro which generally takes four to five weeks. The chimeric epithelium of the present invention is composed of cells that are both autologous and allogeneic to the host. Therefore, the allogeneic cells can be maintained in a cell bank and co-cultured with autologous host cells when needed. This significantly reduces the time required (by up to 50%) for autologous cell expansion and culture prior to grafting. Furthermore, it has been demonstrated that the allogeneic cells are passively eliminated from the graft without rejection of the total graft.

Abstract: The invention includes methods for increasing the efficiency of transduction of cells, including non-dividing cells, by recombinant AAV vectors. The methods utilize agents that alter certain aspects of DNA metabolism, more specifically, that affect DNA synthesis and/or affect repair, that impact on maintenance of chromosomal integrity, and/or that cause damage to the cellular DNA. Agents and vectors can now also be preselected and screened for transducing ability and/or transducing agents for their effect on DNA metabolism. These agents include tritiated nucleotides such as thymidine, gamma irradiation, UV irradiation, cis-platinum, etoposide, hydroxyurea and aphidicolin.

Abstract: Cis-acting repression sequences which are able to provide a cis-acting inhibitory effect on the expression of a gene when placed downstream of the gene in its untranslated message are dislcosed. Cis-acting anti-repression sequences which can relieve the cis-acting repression in the presence of the art gene product are also disclosed. These sequences correspond to a sufficient number of nucleotides from the HIV-I, HIV-2, STLV-3 or HTLV-IV genomes to provide the repression or anti-repression effects. The use of the sequences in vectors and systems to control the expression of a desired gene product is also described.

Abstract: Methods of prophylactic and therapeutic immunization of an individual against pathogen infection, diseases associated with hyperproliferative cells and autoimmune diseases are disclosed. The methods comprise the steps of administering to cells of an individual, a nucleic acid molecule that comprises a nucleotide sequence that encodes a protein which comprises at least one epitope that is identical or substantially similar to an epitope of a pathogen antigen, a hyperproliferative cell associated protein or a protein associated with autoimmune disease respectively. In each case, nucleotide sequence is operably linked to regulatory sequences to enable expression in the cells. The nucleic acid molecule is free of viral particles and capable of being expressed in said cells. The cells may be contacted cells with a cell stimulating agent. Methods of prophylactically and therapeutically immunizing an individual against HIV are disclosed.

Abstract: Genetically engineered human stem cells that carry within them genes of interest particularly for the expression of physiologically or pharmacologically active proteins or for use in gene therapy. In addition to correction of genetic disorders, is the ability to introduce, in a targeted manner, additional copies of essential genes to allow expression in proliferating, nondifferentiating cells of certain gene products. These genes can be, for example, hormones matrix proteins, cytokines, adhesion molecules, detoxification enzymes and "rebuilding" proteins important in tissue repair.

Abstract: The invention described herein allows the production of recombinant retroviruses (retroviral vector particles) from producer cells which are safer and of higher titer than normal. In addition, methods are provided for making helper cells which, when a recombinant retrovirus genome is introduced to make a producer line, produce particles that are targeted toward particular cell types. Methods are also provided for making recombinant retrovirus systems adapted to infect a particular cell type, such as a tumor, by binding the retrovirus or recombinant retrovirus in the particular cell type. Methods are also provided for producing recombinant retroviruses which integrate in a specific small number of places in the host genome, and for producing recombinant retroviruses from transgenic animals.

Abstract: The invention relates to a defective recombinant retrovirus containing a sequence coding for a specific protein in the genome of the cells. The DNA of the recombinant retrovirus contains the sequence coding for the protein intercalated between an acceptor splicing site and a donor splicing site, the whole assembly being placed under the control of a suitable promoter under conditions such that the infection of the said cells by this recombinant retrovirus is accompanied by the incorporation of the sequence coding for the protein into the genome of the infected cells.

Abstract: In accordance with the present invention, disclosed is a method of conferring, upon a host cell, resistance to retroviral infection by interfering with one or more of the infection processes including retroviral replication and assembly into infective viral particles. The method involves introducing a vector into a host cell, wherein the vector comprises a polynucleotide which directs transcription, within the host cell, of RNA which is a) complementary or corresponding, depending on the target region, to a nucleic acid sequence within one or more regions of the genome of the retrovirus; and b) is effective in inhibiting one or more steps in the retroviral infection process by interfering with retroviral replication, reverse transcription, translation, or assembly into viral particles when the host cell is infected. Also disclosed is a method of treatment using the nucleic acid constructs, or cells upon which resistance to infection has been conferred.

Abstract: This invention provides a unique and surprisingly accurate animal model for human schizophrenia. The animals are brain damaged while prepubescent. The brain damage consists of a ventral hippocampus lesion induced by exposure of the hippocampus region to a neurotoxin. When the animal reaches puberty, abnormal behavior and a number of biological phenomena associated with schizophrenic symptoms emerge. These animals are useful for assaying pharmaceutical compounds for anti-schizophrenic activity.