Abstract: The present invention provides methods for producing a minus-strand RNA viral vector, which comprise using a promoter comprising a cytomegalovirus enhancer and a chicken ?-actin promoter, to induce the transcription of the genome RNA of a minus-strand RNA viral vector and the expression of minus-strand RNA viral proteins that form a ribonucleoprotein with the genome RNA. The methods of the present invention enable high efficiency production of highly safe minus-strand RNA viral vectors. The methods of the present invention are particularly useful for producing minus-strand RNA viral vectors that are deficient in envelope-constituting protein genes.

Abstract: The present invention provides a vaccine containing a Sendai virus vector encoding a virus protein of an immunodeficiency virus. By intranasally administering a Sendai virus encoding a virus protein of an immunodeficiency virus to a macaque monkey, the present inventors have succeeded in efficiently inducing protective immunity against an immunodeficiency virus. As a result of intranasal inoculation of vaccine, expression of an antigen protein mediated by Sendai virus vector was detected in intranasal mucous membrane and local lymph nodes and antigen-specific cellular immune response was induced at a significant level. No pathological symptom by vaccination was observed. After vaccination, exposure of simian immunodeficiency virus was performed and the effect was examined. As a result, the amount of virus in plasma significantly decreased, compared with that of the control animal. The present invention provides a promising vaccine as an AIDS vaccine.

Abstract: The present invention provides Paramyxovirus vectors encoding angiogenic genes and use of the same. The use of Paramyxovirus vectors enables effective transfer of angiogenic genes into individual tissues. FGF2 gene transferred into ischemic tissues in vivo induces expression of angiogenic genes without causing edema, and prevents necrosis due to ischemia. The vectors of the present invention are suitable for gene therapy targeted to ischemic tissues.

Abstract: The present invention provides Paramyxovirus vectors encoding angiogenic genes and use of the same. The use of Paramyxovirus vectors enables effective transfer of angiogenic genes into individual tissues. FGF2 gene transferred into ischemic tissues in vivo induces expression of angiogenic genes without causing edema, and prevents necrosis due to ischemia. The vectors of the present invention are suitable for gene therapy targeted to ischemic tissues.

Abstract: The present invention provides cell fusogenic vectors having replicative ability, whose protease-dependent tropism has been modified. M gene-deficient viral vectors encoding modified F proteins, in which the cleavage site of the F protein of paramyxovirus is modified to be cleaved by different proteases, were produced. In cells transfected with these vectors, the genomic RNA present in the vectors is replicated, and cell fusogenic infection spreads to neighboring cells depending on the presence of other proteases; however, no viral particles are released. The vectors of this invention, encoding the F proteins which are cleaved by proteases whose activity is enhanced in cancer, show cancer growth suppressive effect in vivo.

Abstract: The present invention provides a vaccine containing a Sendai virus vector encoding a virus protein of an immunodeficiency virus. By intranasally administering a Sendai virus encoding a virus protein of an immunodeficiency virus to a macaque monkey, the present inventors have succeeded in efficiently inducing protective immunity against an immunodeficiency virus. As a result of intranasal inoculation of vaccine, expression of an antigen protein mediated by Sendai virus vector was detected in intranasal mucous membrane and local lymph nodes and antigen-specific cellular immune response was induced at a significant level. No pathological symptom by vaccination was observed. After vaccination, exposure of simian immunodeficiency virus was performed and the effect was examined. As a result, the amount of virus in plasma significantly decreased, compared with that of the control animal. The present invention provides a promising vaccine as an AIDS vaccine.

Abstract: The present invention provides Paramyxovirus vectors encoding angiogenic genes and use of the same. The use of Paramyxovirus vectors enables effective transfer of angiogenic genes into individual tissues. FGF2 gene transferred into ischemic tissues in vivo induces expression of angiogenic genes without causing edema, and prevents necrosis due to ischemia. The vectors of the present invention are suitable for gene therapy targeted to ischemic tissues.

Abstract: The present invention provides cell fusogenic vectors having replicative ability, whose protease-dependent tropism has been modified. M gene-deficient viral vectors encoding modified F proteins, in which the cleavage site of the F protein of paramyxovirus is modified to be cleaved by different proteases, were produced. In cells transfected with these vectors, the genomic RNA present in the vectors is replicated, and cell fusogenic infection spreads to neighboring cells depending on the presence of other proteases; however, no viral particles are released. The vectors of this invention, encoding the F proteins which are cleaved by proteases whose activity is enhanced in cancer, show cancer growth suppressive effect in vivo.

Abstract: The present invention provides methods for treating tumors, which comprise the step of administering into tumor sites a minus-strand RNA viral vector encoding an immunostimulatory cytokine or cells introduced with the vector. The present invention also provides compositions for treating tumors, which comprise as an active ingredient the minus-strand RNA viral vector encoding an immunostimulatory cytokine or cells introduced with the vector. The present invention also provides kits for treating tumors, which comprise the minus-strand RNA viral vector encoding an immunostimulatory cytokine, and a tumor antigen or a vector expressing the antigen.

Abstract: The present invention provides a retroviral vector containing a membrane protein having a hemagglutinin activity. The present inventors constructed a retroviral vector pseudotyped by the membrane protein having a hemagglutinin activity. This viral vector showed gene transfer at a high efficiency into host cells. In particular, it was established that genes can be transferred thereby at a high efficiency into cells into which genes can hardly be transferred by the conventional techniques, for example, blood cells and hematopoietic cells including hematopoietic stem cells, and mucous cells including mucosa epithelial cells. The viral vector of the present invention is highly useful as a vector for gene therapy.

Abstract: The present invention provides cell fusogenic vectors having replicative ability, whose protease-dependent tropism has been modified. M gene-deficient viral vectors encoding modified F proteins, in which the cleavage site of the F protein of paramyxovirus is modified to be cleaved by different proteases, were produced. In cells transfected with these vectors, the genomic RNA present in the vectors is replicated, and cell fusogenic infection spreads to neighboring cells depending on the presence of other proteases; however, no viral particles are released. The vectors of this invention, encoding the F proteins which are cleaved by proteases whose activity is enhanced in cancer, show cancer growth suppressive effect in vivo.

Abstract: A method for regenerating Sendai virus particles by transfecting the Sendai virus genome to a host expressing all genes for the initial viral replication has been developed, enabling the genetic manipulation of Sendai virus and effective utilization of said virus as the vector.

Abstract: The present invention provides methods for suppressing tumor proliferation comprising the step of inhibiting the expression of PDGF-A or the binding between PDGF-A homodimers and PDGFR?. Activation of the PDGFR?-p70S6K signal transduction pathway by PDGF-AA is an important factor in tumor angiogenesis and relates to the prognosis of patients suffering from tumors. By inhibiting PDGF-A expression in tumors or in their surrounding tissues, or by inhibiting the binding between PDGF-A homodimers and PDGFR?, the formation and retention of tumor vasculature can be inhibited, thereby suppressing tumor proliferation.

Abstract: The present invention provides cell fusogenic vectors having replicative ability, whose protease-dependent tropism has been modified. M gene-deficient viral vectors encoding modified F proteins, in which the cleavage site of the F protein of paramyxovirus is modified to be cleaved by different proteases, were produced. In cells transfected with these vectors, the genomic RNA present in the vectors is replicated, and cell fusogenic infection spreads to neighboring cells depending on the presence of other proteases; however, no viral particles are released. The vectors of this invention, encoding the F proteins which are cleaved by proteases whose activity is enhanced in cancer, show cancer growth suppressive effect in vivo.

Abstract: Minus-strand RNA viruses were found to have an effective tumor-suppressive effect even when they did not carry a therapeutically effective gene. The present invention provides anticancer agents comprising a minus-strand RNA virus. Furthermore, the present invention provides methods for producing the anticancer agents, which comprise the step of mixing a minus-strand RNA virus with pharmaceutically acceptable carriers. Furthermore, the present invention provides methods for suppressing cancer, which comprise the step of administering a minus-strand RNA virus to cancer tissues.

Abstract: Highly efficient gene transfer into primate-derived embryonic stem (ES) cells has successfully been achieved by using a simian immunodeficiency virus vector (SIV) pseudotyped with VSV-G protein, which is a surface glycoprotein of vesicular stomatitis virus (VSV) The present invention provides simian immunodeficiency virus vectors for gene transfer to primate ES cells. The method for gene transfer to primate ES cells using the vectors of the present invention is useful in, for example, research into embryology and disease, clinical applications, and experimental models for primates. The method is also useful in assaying and screening for genes and reagents able to enhance the specific differentiation of tissues or cells, and which are useful in preparing desired cells or tissues differentiated from ES cells.

Abstract: The present invention provides anticancer agents comprising dendritic cells introduced with RNA viruses. The present invention also provides methods for producing anticancer agents, which comprise the step of preparing dendritic cells introduced with RNA viruses. The present invention also provides methods for treating cancers using dendritic cells introduced with RNA viruses.

Abstract: Provided are a recombinant Sendai virus vector for introducing exogenous genes to airway epithelia and a method for introducing exogenous genes using the vector. The recombinant Sendai virus vector enables efficient gene transfer to native mucus-layered airway epithelial cells by briefly contacting the vector with the cells. Furthermore, the vector can introduce genes to not only apical surfaces but also submucosal glands where CFTR primarily expresses. The vector can thus be used for gene therapy of CF, a CFTR-deficient disease.

Abstract: The present invention provides methods for treating tumors, which comprise the step of administering into tumor sites a minus-strand RNA viral vector encoding an immunostimulatory cytokine or cells introduced with the vector. The present invention also provides compositions for treating tumors, which comprise as an active ingredient the minus-strand RNA viral vector encoding an immunostimulatory cytokine or cells introduced with the vector. The present invention also provides kits for treating tumors, which comprise the minus-strand RNA viral vector encoding an immunostimulatory cytokine, and a tumor antigen or a vector expressing the antigen.

Abstract: Use of a negative-sense RNA virus vector has enabled transfer of nucleic acid into nerve cells. The method of this invention can be used for introducing a gene efficiently into nerve cells including the central nerve tissue in gene therapy, etc.