Abstract: The present invention provides mutant viruses with a decreased ability to block nuclear transport of mRNA or protein in an infected cell which are attenuated in vivo. The mutant viruses of the present invention may also be capable of triggering the anti-viral systems of normal host cells while remaining sensitive to the effects of these systems. The present invention further provides for the use of the mutant viruses in a range of applications including, but not limited to, as therapeutics for the treatment of cancer and infections, as vaccines and adjuvants, as viral vectors, and as oncolytic and cytolytic agents for the selective lysis of malignant or infected cells.

Abstract: BIV packaging constructs, BIV packaging cell lines, methods of making BIV packaging cells and methods of making BIV producer cells are described.

Abstract: The present invention relates to therapeutic use of Myxoma virus. Myxomas virus can selectively infect cells that have a deficient innate anti-viral response, including cells that are not responsive to interferon and can be used to treat diseases characterized by the presence of such cells, including cancer.

Abstract: The present invention is directed to a method of reducing the viability of a tumor cell involving administering a virus that is not a common human pathogen to the tumor cell. Preferably, the virus exhibits differential susceptibility, in that normal cells are not affected by the virus. This differential susceptibility is more pronounced in the presence of interferon. The tumor cell is characterized by having low levels, or no, PKR activity, or as being PKR?/?, STAT1?/? or both PKR?/? and STAT1?/?. The virus is selected from the group consisting of Rhabdovirus and picornavirus, and preferably is vesicular stomatitis virus (VSV) or a derivative thereof.

Abstract: A method of treating a human subject with cancer is disclosed. A pharmaceutical composition is administered to the subject, the pharmaceutical composition comprising human leukocytes and a replication-competent oncolytic virus in suspension in a physiologically acceptable solution. Alternatively the pharmaceutical composition comprises human leukocytes or platelets infected with an oncolytic virus.

Abstract: The subject invention relates to viruses that are able to replicate and thereby kill neoplastic cells with a deficiency in the IFN-mediated antiviral response, and their use in treating neoplastic disease including cancer and large tumors. RNA and DNA viruses are useful in this regard. The invention also relates to methods for the selection, design, purification and use of such viruses for cancer therapy.

Abstract: The subject invention relates to viruses that are able to replicate and thereby kill neoplastic cells with a deficiency in the IFN-mediated antiviral response, and their use in treating neoplastic disease including cancer and large tumors. RNA and DNA viruses are useful in this regard. The invention also relates to methods for the selection, design, purification and use of such viruses for cancer therapy.

Abstract: The subject invention relates to viruses that are able to replicate and thereby kill neoplastic cells with a deficiency in the IFN-mediated antiviral response, and their use in treating neoplastic disease including cancer and large tumors. RNA and DNA viruses are useful in this regard. The invention also relates to methods for the selection, design, purification and use of such viruses for cancer therapy.

Abstract: Mammalian subjects having a neoplasm are treated with a virus, a fluoropyrimidine, for example 5-fluorouracil, and a camptothecin compound. The virus is selected from the group consisting of a Newcastle disease virus, a measles virus, a vesicular stomatitis virus, an influenza virus, a Sindbis virus, a picornavirus, and a myxoma virus.

Abstract: The invention provides a method of treating cancer in a mammal comprising administering to the mammal an effective amount of virus, particularly Newcastle Disease Virus or other Paramyxovirus. The invention also provides a method of treating cancer in a mammal comprising administering such viruses to the mammal in combination with another agent such as a chemotherapeutic compound, immunoadjuvant, cytokine, or immunosuppressive agent. The invention further provides a method of detecting cancer cells in a mammal using Paramyxovirus as an imaging agent and as an indicator of cancer cell growth in the mammal. The invention further provides genetically engineered Paramyxoviruses, and kits containing the viral compositions disclosed by the invention.

Abstract: The present invention provides mutant viruses with a decreased ability to block nuclear transport of mRNA or protein in an infected cell which are attenuated in vivo. The mutant viruses of the present invention may also be capable of triggering the anti-viral systems of normal host cells while remaining sensitive to the effects of these systems. The present invention further provides for the use of the mutant viruses in a range of applications including, but not limited to, as therapeutics for the treatment of cancer and infections, as vaccines and adjuvants, as viral vectors, and as oncolytic and cytolytic agents for the selective lysis of malignant or infected cells.

Abstract: A method of treating a human subject with cancer is disclosed. A pharmaceutical composition is administered to the subject, the pharmaceutical composition comprising human leukocytes and a replication-competent oncolytic virus in suspension in a physiologically acceptable solution. Alternatively the pharmaceutical composition comprises human leukocytes or platelets infected with an oncolytic virus.

Abstract: The present invention relates to therapeutic use of Myxoma virus. Myxoma virus can selectively infect cells that have a deficient innate anti-viral response, including cells that are not responsive to interferon and can be used to treat diseases characterized by the presence of such cells, including cancer.

Abstract: The present invention provides novel cell lines that may have improved adhesive qualities, transgene expression level, growth rate, and/or growth rate in serum free medium or even chemically defined compared to cells of the prior art.

Abstract: An adenoviral vector including at least one DNA sequence encoding a clotting factor, such as, for example, Factor VIII, or Factor IX. Such vectors may be administered to a host in an amount effective to treat hemophilia in the host. The vectors infect hepatocytes very efficiently, whereby the hepatocytes express the DNA sequence encoding the clotting factor.

Abstract: The invention generally relates to cell-specific expression vectors. It particularly relates to targeted gene therapy using recombinant expression vectors and particularly adenovirus vectors. The invention specifically relates to replication-conditional expression vectors and methods for using them. Such vectors are able to selectively replicate in a target cell or tissue to provide a therapeutic benefit in a tissue from the presence of the vector per se or from one or more heterologous gene products expressed from the vector and distributed throughout the tissue. In such vectors, a gene essential for replication is placed under the control of a heterologous tissue-specific transcriptional regulatory sequence. Thus, replication is conditioned on the presence of a factor(s) that induces transcription or the absence of a factor(s) that inhibits transcription of the gene by means of the transcriptional regulatory sequence with this vector; therefore, a target tissue can be selectively treated.

Abstract: The invention provides novel retroviral vectors that have enhanced transcription termination structures. The termination structures comprise one or several heterologous upstream transcription termination enhancer (UE) sequences, or one or more additional copies of endogenous UE sequences operably associated with the 3′ LTR polyadenylation signal. The retroviral vectors of the invention have various improved properties over conventional vectors, including stronger gene expression, enhanced vector titer and reduced interference with host cell gene expression resulting from read-through of vector initiated transcriptional events.

Abstract: A method of inducing blood vessel formation in an animal by administering to the animal a polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof. The polynucleotide may be contained in an appropriate expression vector, such as a viral vector. The delivery of sphingosine kinase through administration of an expression vector which expresses sphingosine kinase provides for the formation of larger blood vessels containing a well defined structure that is supported by mural cells such as pericytes and smooth muscle cells.

Abstract: The invention generally relates to targeted gene therapy using recombinant vectors and particularly adenovirus vectors. The invention specifically relates to replication-conditional vectors and methods for using them. Such vectors are able to selectively replicate in a target tissue to provide a therapeutic benefit from the presence of the vector per se or from heterologous gene products expressed from the vector and distributed throughout the tissue. In such vectors, a gene essential for replication is placed under the control of a heterologous tissue-specific transcriptional regulatory sequence. Thus, replication is conditioned on the presence of a factor(s) that induces transcription or the absence of a factor(s) that inhibits transcription of the gene by means of the transcriptional regulatory sequence with this vector, therefore, a target tissue can be selectively treated.

Abstract: Immunocompromised mammalian hosts are sub-cutaneously implanted with a combination of human fetal bone and spleen. The chimeric animals can produce human B-cells, myeloid cells and T-cells for up to 9 months in vivo when supplied with an allogeneic human fetal thymic fragment at the same site. Grafts contain cell populations expressing CD4 and CD8, CD19 or CD33, CD14 and CD15, all of which also express the HLA type of the fetal bone/spleen. T-cells derived from progenitors in the fetal bone/spleen contain both mature single positive CD4+CD8−, CD8+CD4− as well as a high percentage of immature double positive CD4+CD8+ populations.