Abstract: This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention.

Abstract: The present invention provides recombinant nucleic acid molecules encoding a chimeric transactivator protein including a DNA binding domain of a DNA binding protein and a protein domain capable of transcriptional activation. The present invention also provides recombinant viral and non-viral vectors that are able to infect and/or transfect and sustain expression of a biologically active chimeric transactivator proteins in mammalian cells. Also provided are host cell lines and non-human transgenic animals capable of expressing biologically active chimeric transactivator proteins. In another aspect, compositions and methods for treating or preventing ischemic damage associated with hypoxia-related disorders are provided.

Abstract: Fusions of the transcription factor E2F and the retinoblastoma protein RB are provided, along with methods of treatment of hyperproliferative diseases.

Abstract: The present invention relates to transgene expression systems, related compositions comprising the transgene expression systems, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA encoding a transgene which codes for a desired product operably linked to expression control sequence, and at least a portion of the adenovirus E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E40RF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or “E4 cassette”) includes E40RF3 and at least one other portion selected from E40RF4, E40RF6/7 and E40RF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell.

Abstract: The present invention relates to transgene expression systems, related compositions comprising the transgene expression systems, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA encoding a transgene which codes for a desired product operably linked to expression control sequence, and at least a portion of the adenovirus E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E4ORF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or “E4 cassette”) includes E4ORF3 and at least one other portion selected from E4ORF4, E4ORF6/7 and E4ORF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell.

Abstract: This invention provides a method of treating cancer by administering a replication competent adenoviral vector comprising a therapeutic gene and a disease specific gene regulatory region operationally linked to at least one replication gene. The replication competent targeted adenoviral vector preferentially replicates in the tumor cells following activation of the tumor specific gene regulatory region thereby amplifying the effect of the therapeutic gene carried by the replication competent adenoviral vector. This invention enables for the first time the targeting of a therapeutic gene for treating cancer using small amounts of viral vectors which selectively replicate to deliver therapeutic dosages of the therapeutic gene.

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: This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention.

Abstract: This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention.

Abstract: This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine kinase. (The latter must be used in conjunction with a thymidine kinase metabolite in order to be effective).

Abstract: The present invention relates to transgene expression systems, related pharmaceutical compositions, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA sequence encoding a transgene which codes for a desired product, expressibly contained within an adenovirus vector containing at least a portion of the E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E4ORF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or "E4 cassette") includes E4ORF3 and at least one other portion selected from E4ORF4, E4ORF6/7 and E4ORF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.

Abstract: Gene Therapy vectors, which are especially useful for cystic fibrosis, and methods for using the vectors are disclosed.

Abstract: Fusions of the transcription factor E2F and the retinoblastoma protein RB are provided, along with methods of treatment of hyperproliferative diseases.

Abstract: The invention is directed to novel adenoviral vectors which are capable of facilitating persistent expression of a transgene which is delivered by the vector to a cell. The vectors are E1/partial E3 deleted vectors which contain a transgene operably linked to expression control sequences, preferably the CMV promoter. The invention is also directed to compositions comprising the adenoviral vectors of the invention and to methods for providing persistent expression of a transgene to the cells of an individual by administration of the compositions.

Abstract: The invention is directed to a transgene expression system comprising a transcription unit which contains a transgene operably linked to expression control sequences, preferably the CMV promoter, and which is delivered simultaneously with all or part of the adenovirus E4 genomic region to a cell in order to facilitate persistent expression of the transgene. The components of the transgene expression system can be delivered by vectors including plasmids and/or viruses and may be complexed with cationic amphiphiles to facilitate entry into a cell. The invention is also directed to methods for the production of the transgene expression system. The invention is further directed to compositions that contain the transgene expression system and to methods for the use of such compositions to deliver transgenes encoding biologically active proteins to cells.

Abstract: Antibodies for binding epitopes of cystic fibrosis transmembrane conductance regulator (CFTR) and hybridomas which produce such antibodies are described. The antibodies of the present invention can be used in a method for detecting CFTR in a biological sample and/or in a method for purifying CFTR from an impure solution. In addition, the present invention includes a method for detecting CFTR in a biological sample from a nonhuman cystic fibrosis knockout animal wherein the the nonhuman cystic fibrosis knockout animal has been subjected to human CFTR replacement therapy. Another aspect of the present invention is a method for determining the orientation of CFTR in the membrane of a lipid vesicle. Yet another aspect of the invention is a kit for detecting CFTR in a biological sample.

Abstract: This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine kinase. (The latter must be used in conjunction with a thymidine kinase metabolite in order to be effective).

Abstract: Adenoviral vectors which contain deletions of the early regions and/or late genes provide efficient delivery and expression of foreign nucleic acids of interest to patients. These vectors have a particular use in the treatment of cystic fibrosis patients. Furthermore, PAV vectors provide for a second generation of adenoviral vectors that contain the 5' ITR's, the packaging signal and the E1A enhancer. Other adenoviral vectors contain a deletion of the E1 region or a deletion of E4 but retain orf3 or orf6, and can either retain or delete the E3 region.

Abstract: A pharmaceutical composition comprising a vector itself comprising a purified and isolated DNA sequence consisting essentially of a DNA sequence encoding a polypeptide having an amino acid sequence sufficiently duplicative of CFTR to allow possession of the biological property of correction of a defect in epithelial cell anion channel regulation.

Abstract: A chimeric adenoviral vector is provided that comprises nucleotide sequence of a first adenovirus, wherein at least one gene of said first adenovirus encoding a protein that facilitates binding of said vector to a target mammalian cell, or internalization thereof within said cell, is replaced by the corresponding gene from a second adenovirus belonging to subgroup D, said vector further comprising a transgene operably linked to a eucaryotic promoter to allow for expression therefrom in a mammalian cell. Additionally, a method of delivering transgenes to target mammalian cells, particularly airway epithelial cells, is provided.