Abstract: The present invention provides Sendai virus vectors in which genes that encode reprograming factors for inducing pluripotent stem cells are incorporated in a specific order, compositions comprising these vectors for gene delivery to be used in the induction of pluripotent stem cells, and uses thereof. Incorporation of the KLF gene, OCT gene, and SOX gene in a specific order into a single Sendai virus vector successfully and significantly increased the efficiency of pluripotent stem cell induction. Loading multiple reprogramming factors into a single vector can further increase the induction efficiency of pluripotent stem cells while reducing the number of necessary vectors.

Abstract: An objective of the present invention is to provide methods for producing dendritic cells (DCs), which comprise the step of culturing DC precursor cells in the presence of a plurality of cytokines, produced dendritic cells, and uses thereof. The present inventors discovered that dendritic cells with a high IL-12 productivity can be obtained by culturing DC precursor cells in the presence of a plurality of cytokines, followed by about one week of culture in the presence of GM-CSF and IL-4. The present invention enables preparation of a large amount of DCs with a high IL-12 productivity from a small number of DC precursor cells, and therefore makes it easier to increase the number of DCs for administration in DC-based anti-tumor immune therapy, treatment of infections, etc. Thus, the effect of DC vaccines is expected to be enhanced.

Abstract: The present invention provides Sendai virus vectors in which genes that encode reprograming factors for inducing pluripotent stem cells are incorporated in a specific order, compositions comprising these vectors for gene delivery to be used in the induction of pluripotent stem cells, and uses thereof. Incorporation of the KLF gene, OCT gene, and SOX gene in a specific order into a single Sendai virus vector successfully and significantly increased the efficiency of pluripotent stem cell induction. Loading multiple reprogramming factors into a single vector can further increase the induction efficiency of pluripotent stem cells while reducing the number of necessary vectors.

Abstract: The present invention provides novel methods for treating diseases associated with apoptotic degeneration in ocular tissue cells by effective administration of pigment epithelium derived factor (PEDF). The present inventors studied PEDF as a means to prevent ganglion cell death, the final pathology of glaucoma. The present invention is particularly focused on SIV vectors for effective methods for delivering PEDF, and constructed an SIV-PEDF vector. When the SIV-PEDF vector was administered subretinally to an ischemia reperfusion model and NMDA-induced model, a significant suppression effect on ganglion cell death was observed. The present inventors therefore discovered that the SIV-PEDF vector is an effective pharmaceutical agent for treating diseases associated with apoptotic degeneration in ocular tissue cells, such as glaucoma.

Abstract: An objective of the present invention is to provide methods for producing dendritic cells (DCs), which comprise the step of culturing DC precursor cells in the presence of a plurality of cytokines, produced dendritic cells, and uses thereof. The present inventors discovered that dendritic cells with a high IL-12 productivity can be obtained by culturing DC precursor cells in the presence of a plurality of cytokines, followed by about one week of culture in the presence of GM-CSF and IL-4. The present invention enables preparation of a large amount of DCs with a high IL-12 productivity from a small number of DC precursor cells, and therefore makes it easier to increase the number of DCs for administration in DC-based anti-tumor immune therapy, treatment of infections, etc. Thus, the effect of DC vaccines is expected to be enhanced.

Abstract: The present invention uses an RPN2 gene expression inhibitor as a cancer cell growth inhibitor, which further includes a drug showing an anti-cancer action if desired, and is administered in combination with atelocollagen if desired. In addition, the present invention is an anti-cancer agent including such cancer cell growth inhibitor.

Abstract: [Problems to be Solved] The present invention provides methods for producing antibodies and antibody-producing cells. [Means for Solving the Problems] The present invention provides methods for producing antibodies or antibody-producing cells, such methods including the steps of inoculating non-human animals with minus-strand RNA viral vectors carrying nucleic acids which encode foreign polypeptides to be used as antigens, nucleic acids producing the viral vectors, cells into which the vectors or the nucleic acids producing the vectors have been introduced, or lysates of the cells; and collecting the antibodies or antibody-producing cells from the animals. The antibody production can be induced efficiently by the immune activating effect of the minus-strand RNA viral vectors and a high expression of the antigen polypeptides. The antibodies produced by the methods of the present invention can be used in research and development and in the clinical field.

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 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 uses an RPN2 gene expression inhibitor as a cancer cell growth inhibitor, which further includes a drug showing an anti-cancer action if desired, and is administered in combination with atelocollagen if desired. In addition, the present invention is an anti-cancer agent including such cancer cell growth inhibitor.

Abstract: The present invention provides novel methods for treating diseases associated with apoptotic degeneration in ocular tissue cells by effective administration of pigment epithelium derived factor (PEDF). The present inventors studied PEDF as a means to prevent ganglion cell death, the final pathology of glaucoma. The present invention is particularly focused on SIV vectors for effective methods for delivering PEDF, and constructed an SIV-PEDF vector. When the SIV-PEDF vector was administered subretinally to an ischemia reperfusion model and NMDA-induced model, a significant suppression effect on ganglion cell death was observed. The present inventors therefore discovered that the SIV-PEDF vector is an effective pharmaceutical agent for treating diseases associated with apoptotic degeneration in ocular tissue cells, such as glaucoma.

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: 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: 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: F gene-deficient virus virions are successfully recovered by using an F gene-deficient Sendai virus genomic cDNA. Further, F gene-deficient infectious viral particles are successfully constructed by using F-expressing cells as helper cells. Also, F gene and HN gene-deficient virus virions are successfully recovered by using a virus genomic cDNA deficient in both F gene and HN gene. Further, F gene and HN gene-deficient infectious viral particles are successfully produced by using F- and HN-expressing cells as helper cells. A virus deficient in F gene and HN gene and having F protein is constructed by using F-expressing cells as helper cells. In addition, M gene-deficient infectious virus particles were produced using helper cells expressing M protein. From cells infected with M gene-deficient viruses, release of virus-like particles was inhibited. Further, a VSV-G pseudo type virus is successfully constructed by using VSV-G-expressing cells.

Abstract: A functional RNP containing negative-strand single-stranded RNA derived from Sendai virus, which has been modified so as not to express at least one envelope protein, has been successfully prepared. An RNP comprising a foreign gene is prepared and inserted into a cell with the use of a cationic liposome, thereby successfully expressing the foreign gene.

Abstract: The present invention provides a method for transplanting lymphohematopoietic cells into a mammal, which comprises the step of injecting cells into a bone marrow cavity, and wherein the cells have an exogenous gene encoding a receptor that induces cell proliferation in response to ligand binding. By combining intra-bone marrow transplantation (iBMT) and selective amplifier gene (SAG), marrow conditioning before the injection of the cells can be omitted. The present invention further provides a bone marrow transplant and a kit for transplanting lymphohematopoietic cells into mammals. Furthermore, the invention provides an SAG particularly suitable for such transplantation.

Abstract: The present invention provides methods for producing a viral vector comprising a membrane protein that binds to sialic acid as a component of the envelope, using neuraminidase (NA) derived from Gram-positive bacteria. The methods comprise the steps of culturing cells producing a viral vector in the presence of an NA from Gram-positive bacteria, and recovering the produced virus. The methods of this invention enable the production of high titer virus at high cost performance. Such a viral vector is capable of transferring genes at high efficiency into cells such as blood cells and hematopoietic cells, including hematopoietic stem cells, and mucous cells including mucoepithelial cells, those not amenable to gene transfer by conventional methods, and therefore should be useful as a vector for gene therapy.

Abstract: The present invention provides pharmaceutical- or gene-carrier compositions with reduced hemagglutinating activity. By attaching a compound to a minus-strand RNA virus envelope protein having hemagglutinating activity, a pharmaceutical- or gene-carrier composition with lower hemagglutinating activity than a composition to which the compound has not been attached can be successfully constructed. For example, an embodiment of the present invention provides a viral vector whose erythrocyte agglutination activity and hemolytic activity are significantly lowered, and whose stability in blood is remarkably elevated. The pharmaceutical- or gene-carrier compositions provided in this invention can be preferably used for transferring pharmaceuticals or genes in vivo.