Dna Vec Research Inc.

Id Pharma Co., Ltd.

Dnavec Corporation

Other

Keio University

National Center for Global Health and Medicine

Japan, as Represented by the Director-General of National Institute of Infectious Disease

Mamoru Hasegawa

Yoshikazu Yonemitsu

Makoto Inoue

Akihiro Iida

Tsuneaki Sakata

Yoshiyuki Nagai

Atsushi Kato

Yasuji Ueda

Hiroshi Ban

Mahito Nakanishi

Tatsuo Shioda

Teruo Akuta

Fukashi Murai

Makoto Asakawa

Noemi Fusaki

Katsuo Takeda

Masanori Kobayashi

Katsuo Sueishi

Emi Nagoshi

Toshihiro Nakajima

Koichi Saeki

Hiroyuki Mano

Masayuki Fukumura

Hiroaki Kinoh

Kenji Nakamaru

Takahiro Hirata

Tsuyoshi Tokusumi

Fuyuki Ishikawa

Toshiaki Tabata

Keiichi Fukuda

Hitoshi Iwasaki

Katsuyuki Mitomo

Yui Harada

Shinsuke Yuasa

Masanori Miyazaki

Tsugumine Shu

Shinji Okano

Uta Griesenbach

Yasuhiro Ikeda

Tetsuro Matano

Akira Yuo

Xiaogang Hou

Miwako Nishio

Hidenori Matsusaka

Masako Kawasaki

Hiroyuki Tsutsui

Yasuo Iwadate

Akira Yamaura

Tomohisa Seki

Hiroyuki Sakakibara

Eric W F W Alton

Masayuki Shirakura

Satoko Shibata

Kaio Kitazato

Hidekazu Kuma

Haruhiko Kondo

Fumino Tokito

Yumiko Tokusumi

Masanori Hayami

Eric W Alton

Eiji Ido

Hajime Okuyama

Haruhiko Yokoi

Kumiko Saeki

Munehide Kano

Tatsuo Muramatsu

Jun You

An objective of the present invention is to provide vectors for conveniently and efficiently producing ES-like cells in which foreign genes are not integrated into the chromosome. The present inventors discovered methods for producing ES-like cells from somatic cells using chromosomally non-integrating viral vectors. Since no foreign gene is integrated into the chromosome of the produced ES-like cells, they are advantageous in tests and research, and immunological rejection and ethical problems can be avoided in disease treatments.

Method for production of reprogrammed cell using chromosomally unintegrated virus vector

The present invention provides methods for improving the efficiency of inducing pluripotent stem cells, as well as vectors and compositions for use therein. In the induction of pluripotent stem cells which contains the step of introducing a vector that contains the KLF gene, OCT gene, and SOX gene in this order, the efficiency of pluripotent stem cell induction was successfully increased significantly by further introducing a vector that contains the KLF gene but not the OCT gene and the SOX gene. The methods of the present invention have an excellent feature in that they allow efficient induction of pluripotent stem cells under a temperature condition closer to the physiological environment, and prompt vector removal after the pluripotent stem cell induction. The present invention enables more efficient induction of pluripotent stem cells.

Method for improving efficiency of inducing pluripotent stem cell

The present inventors successfully introduced genes into stem cells of airway epithelial tissues using simian immunodeficiency virus vectors pseudotyped with F and HN, which are envelope glycoproteins of Sendai virus. Gene transfer into airway epithelial tissue stem cells using a vector of the present invention is useful for gene therapy of genetic respiratory diseases such as cystic fibrosis. Furthermore, it is possible to select respiratory organs such as the lungs as production tissues for providing proteins that are deficient due to genetic diseases.

Gene transfer into airway epithelial stem cell by using lentiviral vector pseudotyped with RNA virus or DNA virus spike protein

Provided are a method of producing brown adipocytes from pluripotent stem cells, a method of producing cell aggregates as an intermediate product thereof, pluripotent stem cell-derived cell aggregates and pluripotent stem cell-derived brown adipocytes produced by these methods, and cell therapy using the pluripotent stem cell-derived brown adipocytes. In the method of producing brown adipocytes from pluripotent stem cells, cell aggregates are produced from pluripotent stem cells by a method including the step (A), and brown adipocytes are prepared from the cell aggregates by a method including the step (B). The step (A) is a step of producing cell aggregates by non-adhesive culture of pluripotent stem cells in serum-free environment in the presence of a hematopoietic cytokine, and the step (B) is a step of producing brown adipocytes by adhesion culture of the cell aggregates in the presence of a hematopoietic cytokine.

Pluripotent stem cell-derived brown adipocytes, pluripotent stem cell-derived cell aggregate, method for producing same, and cell therapy and medical therapy therefor

An object of the present invention is to provide methods for producing iPS cells with low invasivity and high efficiency. The iPS cells can be produced with high efficiency using a method comprising the steps of culturing mononuclear cells derived from peripheral blood for 3 to 14 days in the presence of anti-CD3 antibody, and subjecting the cultured mononuclear cells to dedifferentiation.

Method for producing induced pluripotent stem cells

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.

Composition for inducing pluripotent stem cell, and use thereof

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. The present invention provides effective methods for treating cancers, which use RNA viruses and dendritic cells in combination.

Anticancer agent containing dendritic cell having RNA virus transferred thereinto

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 &#x3b2;-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.

Methods for producing minus-strand RNA viral vectors using hybrid promoter comprising cytomegalovirus enhancer and chicken &#x3b2;-actin promoter

The present invention provides methods for producing DCs, which comprise the step of culturing DC precursor cells in the presence of multiple cytokines, dendritic cells produced thereby, and uses thereof. The methods of the present invention enable production of large quantities of DC precursors with a high ability to differentiate into DCs. The present invention enables one to obtain large quantities of DCs 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 immunotherapy, treatment of infection, and such. Thus, an enhancement is expected for the effect of DC vaccines.

Method for production of dendritic cell

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.

Therapeutic agents for diseases associated with apoptotic degeneration in ocular tissue cells that use SIV-PEDF vectors

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.

AIDS virus vaccines using Sendai virus vector

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.

Paramyxovirus vector encoding angiogenesis gene and use thereof

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.

Vectors with modified protease-dependent tropism

Growing community of inventors

Ibaraki, Japan

Mamoru Hasegawa