Abstract: The present invention is directed to the use of benzimidazole derivatives for the treatment of tumors and in combination with tumor suppressor gene therapy. In a particular embodiment, treatment of p53-positive tumors with benzimidazole derivatives induces p53 expression and increases its half-life, resulting in apoptotic death of the tumor cells. Similarly, in conjunction with p53 gene therapy, benzimidazole derivatives induce p53 expression and accumulation in tumor cells regardless of their p53 status. The combination treatment subsequently elicits apoptosis of the tumor cells.

Abstract: Embodiments of the invention include methods and compositions including viral composition that have high transduction efficiencies in vivo, in vitro and ex vivo. The viral composition include a viral vector and a protamine molecule, wherein the viral vector includes a polynucleotide encoding a tumor suppressor gene. The methods of the invention include administering the viral composition to a patient or subject for treatment of disease, in particular cancer, that is characterized by a reduced vector-induced production of neutralizing antibodies and a decreased vector-induced toxicity as compared to delivery of viral vectors alone.

Abstract: Described are simplified and efficient methods for preparing recombinant adenovirus using liposome-mediated cotransfection and the direct. observation of a cytopathic effect (CPE) in the transfected cells. Also disclosed are compositions and methods involving novel p53 adenovirus constructs, including methods for restoring p53 function and tumor suppression in cells and animals having abnormal p53.

Abstract: An adenoviral supervector system is disclosed that is capable of expressing more than 7.5 kilobases of heterologous DNA in a replication defective adenoviral vector. The supervector system comprises an adenoviral vector construct and a helper cell. The vector construct is capable of being replicated and packaged into a virion particle in the helper cell. In particular, the helper cell expresses DNA from the E2 region of the adenovirus 5 genome and complements deletions in that region in the vector construct. In certain embodiments, the disclosed invention comprises tissue specific expression of up to 30 kb of heterologous DNA directed by an adenoviral vector. Also disclosed are methods of transferring heterologous DNA into mammalian cells.

Abstract: The present invention provides viral vectors that have been engineered to contain a synthetic promoter that controls at least one essential gene. The synthetic promoter is induced by a specific gene product not normally produced in the cells in which the viral vector is to be transferred. The vectors are propagated in producer or helper cells that express the inducing factor, thereby permitting the virus to replicate to high titer. The lack of the inducing factor in the target cells precludes viral replication, however, meaning that no vector toxicity or immunogenicity arises. Where the virus carries a gene of interest, this should provide for higher level expression for longer periods of time than with current vectors. Methods for making the vectors, helper cells, and their use in protein production, vaccines and gene therapy are disclosed.

Abstract: Promoters that include a tissue-selective promoter sequence and a second promoter sequence operatively coupled to the tissue-selective promoter sequence, wherein the second promoter sequence includes a minimal viral promoter sequence, are disclosed. Nucleic acids and compositions that include these promoter sequences are also disclosed. Also disclosed are methods of improving the function of a tissue-selective promoter, involving operatively coupling a tissue-selective promoter sequence with a second promoter sequence that includes a minimal viral promoter sequence. Also disclosed are methods of delivering a gene into a cell, methods of treating a subject with a hyperproliferative disease, and methods of imaging a cell that involve use of the novel promoter sequences set forth herein.

Abstract: A variety of genetic constructs are disclosed that will find both in vitro and in vivo use in the area of tumor biology and cancer therapy. In particular, expression constructs are provided that contain a p16 encoding region and other regulatory elements necessary for the expression of a p16 transcript. One version of the expression construct is a replication-deficient adenoviral vector. Also provided are methods for the transformation of cell lines and the inhibition of cancer cell proliferation.

Abstract: A nanoparticle-polypeptide complex comprising a bioactive polypeptide in association with a nanoparticle, wherein the bioactive polypeptide is modified by the addition of a chemical moiety that facilitates cellular uptake of the protein. The polypeptide can be a protein or a peptide. In some embodiments, the amino acid sequence of the protein or peptide is derived from the amino acid sequence of a tumor suppressor gene product.

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: 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: Described are simplified and efficient methods for preparing recombinant adenovirus using liposome-mediated cotransfection and the direct observation of a cytopathic effect (CPE) in the transfected cells. Also disclosed are compositions and methods involving novel p53 adenovirus constructs, including methods for restoring p53 function and tumor suppression in cells and animals having abnormal p53.

Abstract: The present invention concerns cancer therapy employing an expression construct that affects regulation of one or more particular nucleic acid sequences that encodes a gene product to which an agent is then targeted. In specific embodiments, the present invention relates to the use of p53 gene therapy to treat cancers in combination with Erbitux™(cetuximab). Viral and non-viral gene delivery systems are disclosed.

Abstract: Disclosed are methods and compositions for the selective manipulation of gene expression through the preparation of retroviral expression vectors for expressing antisense sequences, such as K-ras oncogene antisense sequences, or sequences encoding a desired product, such as wild type p53 sequences. Preferred retroviral vectors of the present invention incorporate the ?-actin promoter in a reverse orientation with respect to retroviral transcription. Preferred antisense RNA constructs of the present invention employ the use of antisense intron DNA corresponding to distinct intron regions of the gene whose expression is targeted for down-regulation. In an exemplary embodiment, a human lung cancer cell line (NCI-H460a) with a homozygous spontaneous K-ras mutation was transfected with a recombinant plasmid that synthesizes a genomic segment of K-ras in antisense orientation. Translation of the mutated K-ras mRNA was specifically inhibited, whereas expression of H-ras and N-ras was unchanged.

Abstract: The present invention generally relates to viral vectors and their use as expression vectors for transforming human cells, both in vitro and in vivo. More particularly, the present invention relates to adenoviral vectors containing propapoptotic genes and their use in cancer therapy.

Abstract: Methods to prevent or reduce inflammation secondary to administration of a lipid-nucleic acid complex in a subject, that include administering to the subject a non-steroidal anti-inflammatory agent, a salicylate, an anti-rheumatic agent, an antihistamine, or an immunsuppressive agent with the lipid-nucleic acid complex are disclosed. Also disclosed are methods of screening for inhibitors of the inflammatory response associated with administration of a lipid-nucleic acid complex to a subject, including providing a candidate substance suspected of preventing or inhibiting the inflammation associated with administration of a lipid-nucleic acid complex to the subject. Also disclosed are compositions that include a lipid, a nucleic acid, and a non-steroidal anti-inflammatory agent, a salicylate, an anti-rheumatic agent, an antihistamine, or an immunosuppressive agent.

Abstract: Described are simplified and efficient methods for preparing recombinant adenovirus using liposome-mediated cotransfection and the direct observation of a cytopathic effect (CPE) in the transfected cells. Also disclosed are compositions and methods involving novel p53 adenovirus constructs, including methods for restoring p53 function and tumor suppression in cells and animals having abnormal p53.

Abstract: The present invention generally relates to viral vectors and their use as expression vectors for transforming human cells, both in vitro and in vivo. More particularly, the present invention relates to adenoviral vectors containing propapoptotic genes and their use in cancer therapy.

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: The present invention provides viral vectors that have been engineered to contain a synthetic promoter that controls at least one essential gene. The synthetic promoter is induced by a specific gene product not normally produced in the cells in which the viral vector is to be transferred. The vectors are propagated in producer or helper cells that express the inducing factor, thereby permitting the virus to replicate to high titer. The lack of the inducing factor in the target cells precludes viral replication, however, meaning that no vector toxicity or immunogenicity arises. Where the virus carries a gene of interest, this should provide for higher level expression for longer periods of time than with current vectors. Methods for making the vectors, helper cells, and their use in protein production, vaccines and gene therapy are disclosed.

Abstract: Described are simplified and efficient methods for preparing recombinant adenovirus using liposome-mediated cotransfection and the direct observation of a cytopathic effect (CPE) in the transfected cells. Also disclosed are compositions and methods involving novel p53 adenovirus constructs, including methods for restoring p53 function and tumor suppression in cells and animals having abnormal p53.