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: 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 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: Cell specific replication-competent viral vectors comprising a self processing peptide cleavage sequence are provided. The targeted replication-competent viral vectors include two or more co-transcribed genes under transcriptional control of the same heterologous transcriptional regulatory element (TRE), wherein at least a second gene is under translational control of a self processing cleavage sequence or 2A sequence. Exemplary vector constructs may further include an additional proteolytic cleavage site which provides a means to remove the self processing peptide sequence from the viral vector.

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: Colon cancer specific promoter sequences and adenovirus vehicles are provided. 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: 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: The invention provides methods of treating neoplasia using combinations of target cell-specific replication competent adenoviral vectors and chemotherapy, radiation therapy or combinations thereof. The adenoviral vectors are target cell-specific for the particular type of neoplasia for which treatment is necessary and the combination with the chemotherapy and/or radiation leads to synergistic treatment over existing adenoviral therapy or traditional chemotherapy and radiation therapy.

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: 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: Replication-competent adenoviral vectors comprising an EBV-specific transcriptional regulatory element (TRE) operably linked to a gene required for adenovirus replication are provided. By providing for transcriptional initiating regulation dependent upon transcription factors that are only active in specific, limited cell types, virus replication can be restricted to particular target cells. The modified adenovirus may be used as a vehicle for introducing new genetic capability, particularly associated with cytotoxicity for treating neoplasia.

Abstract: Colon cancer specific promoter sequences and adenovirus vehicles are provided. 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: 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 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 methods of treating neoplasia using combinations of target cell-specific replication competent adenoviral vectors and chemotherapy, radiation therapy or combinations thereof. The adenoviral vectors are target cell-specific for the particular type of neoplasia for which treatment is necessary and the combination with the chemotherapy and/or radiation leads to synergistic treatment over existing adenoviral therapy or traditional chemotherapy and radiation therapy.

Abstract: Adenovirus packaging cell lines for growth of E1A/E1B deficient adenovirus that is substantially free of replication competent adenovirus (RCA), are provided. Methods for producing adenovirus substantially free of RCA are also provided, wherein the adenovirus is grown in a cell line containing coding sequences for adenovirus E1A and E1B, are operably linked to promoters that lack polynucleotide sequences sharing substantial sequence identity with the native adenovirus E1A and E1B promoters.

Abstract: The invention provides melanoma cell specific adenovirus vectors, which preferentially replicate in melanoma cells.

Abstract: The invention provides methods of treating neoplasia using combinations of target cell-specific replication competent adenoviral vectors and chemotherapy, radiation therapy or combinations thereof. The adenoviral vectors are target cell-specific for the particular type of neoplasia for which treatment is necessary and the combination with the chemotherapy and/or radiation leads to synergistic treatment over existing adenoviral therapy or traditional chemotherapy and radiation therapy.

Abstract: The invention provides adenoviral vectors (preferably replication competent) comprising both an E3 sequence and at least one adenoviral gene under transcriptional control of a target cell-specific transcriptional response element. These vectors display significantly improved cytotoxicity, which is especially useful in the cancer context, in which selective destruction of target cells is desirable. The invention further provides host cells comprising the vectors. The invention further provides methods of using the adenoviral vectors.

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 methods of treating neoplasia using combinations of target cell-specific replication competent adenoviral vectors and chemotherapy, radiation therapy or combinations thereof. The adenoviral vectors are target cell-specific for the particular type of neoplasia for which treatment is necessary and the combination with the chemotherapy and/or radiation leads to synergistic treatment over existing adenoviral therapy or traditional chemotherapy and radiation therapy.

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.