Abstract: Human fetal neuro-derived cell lines are implanted into host tissues. The methods allow for treatment of a variety of neurological disorders and other diseases. A preferred cell line is SVG.

Abstract: A method of causing production and secretion into the bloodsream of a human patient of a biologically active enzyme for which the human patient suffers a deficiency; the method involves introducing into the human patient donor bone marrow stromal cells which have been transfected with a gene encoding the enzyme, so that the introduced cells can adhere to a bone cavity surface of the patient and produce and secrete the active enzyme.

Abstract: The instant disclosure relates to cochleates comprising a) a biologically relevant molecule component b) a negatively charged lipid component, and c) a divalent cation component. The cochleate has an extended shelf life, even in a desiccated state. Advantageously, the cochleate can be ingested. The biologically relevant molecule can be a polynucleotide.

Abstract: The invention provides a human prostate-specific transcriptional regulatory sequence, polynucleotides 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 contructs.

Abstract: An animal cell is co-transfected with both a recombinant DNA viral vector which bears a promoter, a recombinase gene and a poly(A) sequence and a recombinant DNA viral vector which bears two recombinase-recognizing sequences and which further bears an origin of replication, a promoter, a foreign gene and a poly(A) sequence, each of which is located between the two recombinase-recognizing sequences. Thereafter, in the co-transfected animal cell, a DNA fragment containing the origin of replication, promoter, foreign gene and poly(A) sequence is excised from the vector by the action of a recombinase expressed in the another vector. The DNA fragment forms a circular DNA molecule which autonomously replicates in the co-transfected animal cell due to the origin of replication, whereby the foreign gene is continuously expressed.

Abstract: Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile.

Abstract: The present invention generally relates to methods for treating a host by implanting genetically unrelated cells in the host. More particularly, the present invention provides human fetal neuro-derived cell lines, and methods of treating a host by implantation of these immortalized human fetal neuro-derived cells into the host.

Abstract: The present disclosure relates to the application of genetic engineering to provide artificial .beta. cells, i.e. cells which can secrete insulin in response to glucose. This is achieved preferably through the introduction of one or more genes selected from the insulin gene, glucokinase gene, and glucose transporter gene, so as to provide an engineered cell having all three of these genes in a biologically functional and responsive configuration. Assays for detecting the presence of diabetes-associated antibodies in biological samples using these and other engineered cells expressing diabetes-associated epitopes are described. Also disclosed are methods for the large-scale production of insulin by perfusing artificial .beta. cells, grown in liquid culture, with glucose-containing buffers.

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: Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from ether or ester-linked alkyl groups, and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile.

Abstract: The present invention relates to novel adenovirus vectors for use in gene therapy which are designed to prevent the generation of replication-competent adenovirus (RCA) during in vitro propagation and clinical use. The invention also provides methods for the production of the novel virus vectors. These vectors maximize safety for clinical applications in which adenovirus vectors are used to transfer genes into recipient cells for gene therapy.

Abstract: Host cell specific adenovirus vehicles are provided for transfecting target host cells. By providing for transcriptional initiating regulation dependent upon transcription factors that are only active in specific, limited cell types, virus replication will be restricted to the target cells. The modified adenovirus may be used as a vehicle for introducing new genetic capability, particularly associated with cytotoxicity for treating neoplasia.

Abstract: Viruses or cells are targeted for selective internalization into a target in vive. A molecule Specific for a receptor on the surface of the target cell is introduced onto the surface of the virus or cell. The modified virus or cell binds the receptor in vive and is internalized by the target cell. The method provides vectors for selective delivery of nucleic acids to specific cell types in vivo and a means to alter the tropism of an infectious agent.

Abstract: A method for selectively killing nervous system and peripheral neoplastic cells is provided. Viral vectors are used to selectively express a cytochrome P450 gene in neoplastic cells, whose gene product targets the cells for selective killing, by rendering the cells sensitive to a chemotherapeutic agent.

Abstract: An in vivo assay for determining the potential thrombogenic activity of a test compound entails pre-treating an animal with both a hepatoxin and either a bacterial agent (whole bacteria or bacterial toxins, including endotoxins) or a bacterial agent-induced cytokine, which pre-treatment enhances sensitivity to thrombogenic substances. The sensitized animal can be used in identifying a thrombogenic substance even when it is a weak potentiator of thrombogenesis, and in detecting smaller amounts of a strong potentiator.

Abstract: The present invention relates to novel chimeric transactivating proteins comprising a functional portion of a DNA binding protein and a functional portion of a transcriptional activator protein. The chimeric transactivating proteins of the invention offer a variety of advantages, including the specific activation of expression of genes engineered to comprise transactivator responsive elements, thereby achieving exceptionally high levels of gene expression. Furthermore, in various embodiments of the invention, the transactivator proteins may be used to increase expression of some genes while repressing the expression of others, thus permitting a greater degree of control of gene expression patterns than other currently available systems. In preferred embodiments of the invention, the function of the chimeric transactivator proteins may be induced, for example, by chemical agents (e.g. IPTG) or changes in temperature.

Abstract: Methods for the enhancement of bone marrow stem cell engraftment are provided for use in transplantation therapy and ex vivo gene therapy of a mammal. The methods involve the transplantation of quiescent stem cells for transplantation therapy and quiescent transfected stem cells for ex vivo gene therapy.

Abstract: A DNA molecule encoding a secretable mature epidermal growth factor (EGF) polypeptide is delivered to a skin wound. The cells that take up the recombinant DNA construct express soluble EGF that is secreted into surrounding fluid. The presence of the EGF accelerates, by a statistically significant amount, the healing time of a wound treated in this manner.The DNA molecule can be a genetic construction that expresses an EGF encoding portion that differs from the naturally occurring EGF precursor gene in that the only coding region retained from the precursor gene is that of the mature EGF polypeptide. Amino-terminal EGF-like repeats and the carboxy-terminal hydrophobic sequence that anchors natural EGF to the cell membrane are not present in the genetic construction.

Abstract: A novel method for expressing a protein which comprises: transforming skeletal myoblasts or cardiac myocytes with a DNA sequence comprising a DNA segment encoding a selected gene downstream of the Rous sarcoma virus long terminal repeat or the expression sequence in pRSV, and implanting said skeletal myoblasts or cardiac myocytes into a recipient which then expresses a physiologically effective level of said protein.

Abstract: The invention provides compositions for stabilizing polynucleic acids and increasing the ability of polynucleic acids to cross cell membranes and act in the interior of a cell. In one aspect, the invention provides a polynucleotide complex between a polynucleotide and certain polyether block copolymers. Preferably the polynucleotide complex will further include a polycationic polymer. In another aspect, the invention provides a polynucleotide complex between a polynucleotide and a block copolymer comprising a polyether block and a polycation block. In yet another aspect, the invention provides polynucleotides that have been covalently modified at their 5' or 3' end to attach a polyether polymer segment. In still another aspect, the invention provides certain preferred polycationic polymers.