摘要:
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.
摘要:
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.
摘要:
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.
摘要:
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.
摘要:
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. An adenovirus of the present invention can further comprise a heterologous gene such as a reporter under transcriptional control of a PB-TRE. The adenovirus vectors can be used to detect and monitor samples for the presence of prostate cells as well as to selectively kill malignant cells producing prostate-specific gene products.
摘要:
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.
摘要:
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.
摘要:
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.
摘要:
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.
摘要:
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.