Abstract: Enhancers which preferentially increase the transcription of cis-linked coding sequences in prostate cells are provided. Methods of using DNA constructs comprising the enhancers to control transcription of heterologous polynucleotides are also provided. Delivery vehicles comprising the enhancers and methods of using the vehicles are also provided. Adenovirus vectors in which one or more genes are under transcriptional control of the enhancers of the invention are also provided. Further provided are methods of using the adenovirus vectors of the invention to confer selective cytotoxicity in mammalian cells.

Abstract: The invention provides new urothelial cell specific transcriptional regulatory sequences derived from human uroplakin II (hUPII), as well as polynucleotide constructs such as adenoviral vectors and methods of using hUPII-derived TREs. Additionally, the invention provides adenoviral vectors comprising a gene, preferably an adenovirus gene, under transcriptional control of a urothelial cell-specific transcriptional regulatory element (TRE). These vectors display urothelial cell-specific cytotoxicity, which is especially useful in the context of bladder cancer, in which destruction of these cells is desirable. The invention further provides compositions and host cells comprising the vectors, as well as method of using the adenoviral vectors.

Abstract: Replication-competent adenovirus vectors specific for cells which allow a probasin transcriptional response element (PB-TRE) to function, such as cells which express the androgen receptor (AR), and methods of use of such viruses are provided. These viruses comprise and adenoviral gene under control of a transcription regulatory portion of a PB-TRE, which is in turn dependent upon AR expression. The gene can be, for example, a gene required for viral replication or the adenovirus death protein gene (ADP). The viruses can also comprise at least one additional adenoviral gene under control of at least one additional prostate-specific transcriptional response element, such as that controlling prostate-specific antigen expression (PSA-TRE). Thus, virus replication can be restricted to target cells exhibiting prostate-specific gene expression, particularly prostate carcinoma cells.

Abstract: Replication-competent adenovirus vectors specific for target cells and methods of use of such viruses are provided. These adenoviruses comprise a first adenoviral gene under control of a cell specific heterologous (i.e., non-adenoviral) transcriptional regulatory element (TRE) and at least a second gene under control of a second heterologous TRE, where the heterologous TREs are different from each other in polynucleotide sequence but functional in the same cell. The adenoviral gene can be, for example, a gene required for adenoviral replication. The second gene can be, for example, a second adenoviral gene or a transgene, such as a gene which can contribute to cytotoxicity in the target cell. Adenoviral replication can be restricted to target cells in which the heterologous TREs are functional and thus, the adenovirus vectors can provide selective cytotoxicity to the target cells, particularly neoplastic cells.

Abstract: Methods of reducing pre-existing humoral immunity to a viral immunogenic therapeutic agent such as adenovirus, using immunoapheresis are disclosed. Antibodies specific for the viral immunogenic therapeutic agent are selectively removed from the blood of an individual prior to administration of the viral immunogenic therapeutic agent by reaction extracorporeally with an immunosorbent which specifically binds the antibody. After the antibody is selectively removed from the blood, the blood is reinfused into the patient and the viral immunogenic therapeutic agent is administered. The invention also provides kits and compositions for selective removal of anti-viral antibody.

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: Methods for rapid detection and/or semi-quantitation of anti-adenovirus antibody are disclosed. Anti-adenovirus antibody is detected using a device comprising a membrane with adsorbed antigen which specifically binds anti-adenovirus antibody and an absorbent pad which is contacted with the membrane. By consolidating detection reactions in a confined location and eliminating the need to manually remove input reagents, detection and semi-quantitation is achieved rapidly and conveniently. The invention also provides kits and devices for detection and/or semi-quantitation of anti-adenovirus antibodies.

Abstract: The present invention provides adenoviral vectors comprising cell status-specific transcriptional regulatory elements which confer cell status-specific transcriptional regulation on an adenoviral gene. A “cell status” is generally a reversible physiological and/or environmental state. The invention further provides compositions and host cells comprising the vectors, as well as methods of using the vectors.

Abstract: Adenovirus vectors replication specific for cells expressing &agr;-fetoprotein (AFP) and their methods of use are provided. By providing for a transcriptional initiating regulation dependent upon AFP expression, virus replication is restricted to target cells expressing AFP, particularly hepatocellular carcinoma cells. The adenovirus vectors can be used to detect and monitor samples for the presence of AFP-producing cells as well as to kill selectively malignant cells producing AFP.

Abstract: Replication-competent adenovirus vectors specific for cells which allows a probasin transcriptional response element (PB-TRE) to function, such as cells which express the androgen receptor (AR), and methods of use of such viruses are provided. These viruses comprise an adenoviral gene under control of a transcriptional regulatory portion of a PB-TRE, which is in turn dependent upon AR expression. The gene can be, for example, a gene required for viral replication or the adenovirus death protein gene (ADP). The viruses can also comprise at least one additional adenoviral gene under control of at least one additional prostate-specific transcriptional response element, such as that controlling prostate-specific antigen expression (PSA-TRE). Thus, virus replication can be restricted to target cells exhibiting prostate-specific gene expression, particularly prostate carcinoma cells.

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 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: Screening of compounds for activity toward inhibition of prostate cancer cell proliferation is provided. A cell line containing an expression construct comprising a transciptional initiation region of a prostate specific enhancer from a human glandular kallikrein (hKLK2) gene is employed which can be used in conventional equipment for determining activity of compounds, where the cell line uses a marker whose expression is responsive to therapeutically active compounds.

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: Screening of compounds for activity toward inhibition of prostate cancer cell proliferation is provided. A cell line is employed which can be used in conventional equipment for determining activity of compounds, where the cell line uses a marker whose expression is responsive to therapeutically active compounds.

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: This invention relates to improved methods and novel compositions for enzyme complementation assays for qualitative and quantitative determination of a suspected analyte in a sample. The use of enzyme-acceptor and enzyme-donor polypeptides prepared by recombinant DNA techniques, DNA synthesis or chemical polypeptide synthesis techniques which are capable of interacting to form an active enzyme complex having catalytic activity characteristic of .beta.-galactosidase is described. Both homogeneous and heterogeneous assays utilizing these polypeptides are described.

Abstract: This invention relates to improved methods and novel compositions for enzyme complementation assays for qualitative and quantitative determination of a suspected analyte in a sample. The use of enzyme-acceptor and enzyme-donor polypeptides prepared by recombinant DNA techniques, DNA synthesis or chemical polypeptide synthesis techniques which are capable of interacting to form an active enzyme complex having catalytic activity characteristic of .beta.-galactosidase is described. Both homogeneous and heterogeneous assays utilizing these polypeptides are described.

Abstract: This invention relates to improved methods and novel compositions for enzyme complementation assays for qualitative and quantitative determination of a suspected analyte in a sample. The use of enzyme-acceptor and enzyme-donor polypeptides prepared by recombinant DNA techniques or chemical polypeptide synthesis techniques which are capable of interacting to form an active enzyme complex having catalytic activity characteristic of .beta.-galactosidase is described. Both homogeneous and heterogeneous assays utilizing these polypeptides are described.