Takara Bio Inc.

Mie University

National Center of Neurology and Psychiatry

Nippon Medical School Foundation

Junichi Mineno

Ikunoshin Kato

Tatsuji Enoki

Hideto Chono

Hiroshi Shiku

Toshikazu Nishie

Katsuyuki Dodo

Sachiko Okamoto

Hirofumi Yoshioka

Hiroaki Ikeda

Hikaru Takakura

Masanari Kitagawa

Fuyuko Takashima

Kazuya Matsumoto

Kazutoh Takesako

Yasuhiro Kawano

Hiromi Okuyama

Kazuhisa Shinmura

Yuki Takenaka

Yasushi Katayama

Jun Mitsui

Naoki Saito

Risa Sumioka

Koichi Iwamura

Tomomi Otsuji

Shuhei Sakamoto

Takashi Okada

Kiyozo Asada

Nobuto Koyama

Takao Yoshida

Mitsuko Ideno

Yuki Orito

Hiromi Kinoh

Toshihiro Shodai

Tomoe Egashira

Masao Funakoshi

Daisuke Tomura

Yuki Yamamoto

Hajime Matsumura

Risa Kato

Asako Hatsuyama

Yuka Hirase

Yoshinori Tanaka

Yuko Taguchi

Noritsugu Yabe

Shin-ichi Yamada

Kenji Sakai

Takashi Morimura

Kensuke Sakai

Yoshinori Katayama

Yasunori Amaishi

Koichi Inoue

Mayumi Shimomura

Takahisa Tsukihara

Hironori Okada

Yoko Yamaguchi

Yasuhiro Tosaka

Kenichi Tahara

Ikuei Nukaya

Saori Yamaguchi

The present invention provides a nucleic acid which encodes an adeno-associated virus (AAV) capsid protein mutant that contains a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID Nos. 15 to 62 or a peptide comprising an amino acid sequence produced by substituting, deleting, inserting and/or adding one or several amino acid residues in an amino acid sequence selected from the group consisting of SEQ ID Nos. 15 to 62; DNA comprising the nucleic acid; a cell harboring the DNA; and a method for producing the cell.

AAV mutant having brain-targeting property

In the present invention, lymphocytes are efficiently grown by culturing lymphocytes in the presence of a novel recombinant fibronectin fragment.

Lymphocyte production method

Stem cells can be efficiently proliferated by culturing the stem cells in the presence of a novel recombinant fibronectin fragment.

Fibronectin fragment to be used for stem cell production

The present invention relates to a method for producing endothelial cells, including carrying out: (a) inducing a population of mesoderm-lineage cells containing endothelial progenitor cells from pluripotent stem cells without forming an embryoid body; and (b) culturing the population of mesoderm-lineage cells containing endothelial progenitor cells in the presence of RepSox, in this order. According to the present invention, endothelial cells with high quality can be efficiently produced from pluripotent stem cells. The endothelial cells obtained by the method of the present invention are useful for the production of, for example, a myocardial sheet, and expected to be utilized in the treatment of a heart disease. A myocardial sheet can be produced by mixing the endothelial cells obtained by the method of the present invention with myocardial cells and mural cells and culturing the cells.

Method for producing endothelial cells

The present invention provides: a mutant of adeno-associated virus (AAV) capsid protein, which contains at least one amino acid substitution in PLA2 domain when compared with the amino acid sequence for wild-type AAV capsid protein; a nucleic acid encoding the mutant; a cell containing the nucleic acid; a method for producing a recombinant AAV particle, comprising a step of culturing the cell to produce the recombinant AAV particle; a recombinant AAV particle containing the mutant; a composition containing the recombinant AAV particle; and a method for transferring a gene into a target cell, comprising a step of bringing the recombinant AAV particle into contact with the target cell.

Mutant of adeno-associated virus (AAV) capsid protein

The present invention provides a method for efficiently manufacturing a non-enveloped virus with high purity without laborious operation by cultivating cells having the ability to produce a non-enveloped virus and bringing the cells and an acidic solution into contact with each other. A non-enveloped virus vector manufactured by the method of the present invention and a composition having the non-enveloped viral vector as an active ingredient are very useful as gene transfer methods in the fields of basic research and clinical application gene therapy.

Method for manufacturing non-enveloped virus

Provided are a production method for non-enveloped virus particles which is characterized in that a sample including non-envelopes virus particles is treated with PEG in at least two concentrations; a kit used in said production method; non-enveloped virus particles produced using said production method; and a pharmaceutical composition having the non-envelopes virus particles as an active ingredient.

Production method for non-enveloped virus particles

The invention provides an AAV particle containing an adeno-associated viral (AAV) capsid protein having an amino acid sequence selected from the group consisting of SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 24, and SEQ ID NO: 30 of the sequence listing; a nucleic acid that encodes this capsid protein; DNA containing this nucleic acid; a cell containing this DNA; and a method for producing this cell.

AAV variant

The present invention provides an expression cassette comprising (1) an expression regulatory region having a sequence corresponding to a transcriptional activator-binding region and (2) a nucleic acid encoding a transcriptional activator which is capable of binding to the expression regulatory region, wherein the nucleic acid is operably linked to the expression regulatory region; a method for expressing a target product in a mammalian cell, a method for producing a cell expressing a target product, and a method for producing a target product in a mammalian cell using the expression cassette; and a kit comprising the expression cassette.

Expression cassette

A nucleic acid comprising a transcription regulation sequence whose transcription is induced by a trans-acting factor of a human immunodeficiency virus and a gene encoding a polypeptide having an endoribonuclease activity specific to single-stranded RNA, wherein the gene is located in such a position that the expression of the gene can be regulated by the transcription regulation sequence; a method for production of a cell showing an inhibited replication of a human immunodeficiency virus therein, the method comprising the step of introducing the nucleic acid into a cell; and a method for treatment or prevention of a human immunodeficiency virus infection.

Nucleic acid for treatment or prevention of immunodeficiency virus infection

The present invention addresses the problem of providing cell populations having a high proportion of CD4-positive naive T cells and/or CD4-positive central memory T cells, and a production method thereof. The present invention provides a production method for CD4-positive T cell populations which is characterized by using anti-CD3 antibodies, fibronectin fragments, and Interleukin-4. The method is characterized not only by the attainment of a cell group with a high proportion of CD4-positive naive T cells and/or CD4-positive central memory T cells, but also by a high bulk yield.

Production method for cell populations

Disclosed is a method for enhancing the function of a T cell, which is characterized by inhibiting the expression of programmed death-1 ligand 1 (PD-L1) and/or programmed death-1 ligand 2 (PD-L2) in the T cell. Also disclosed is a function-enhanced T cell which is produced by the function enhancement method. Further disclosed is a therapeutic agent comprising the function-enhanced T cell. The T cell can enhance an immune response to cancer, and is useful in an immunotherapy effective for cancer and the treatment or prevention of infectious diseases and autoimmune diseases.

Method for enhancing a function of a T cell

According to the present invention, an AAV vector having a higher titer compared with those of conventional ones can be produced using a cell into which a nucleic acid capable of expressing miRNA is introduced artificially. An AAV vector produced using the cell and a composition containing the viral vector as an active ingredient are very useful as gene transfer means in the studies or clinical practice of gene therapies.

Cell capable of producing adeno-associated virus vector

The present invention provides a method for producing a virus vector, which involves a step of culturing a cell capable of producing the virus vector in a culture medium containing a retinoic acid compound, a histone deacetylase-inhibiting substance and a substance capable of forming a chelate; and a culture medium for use in the production of a virus vector, which is characterized by containing a retinoic acid compound, a histone deacetylase-inhibiting substance and a substance capable of forming a chelate as active ingredients.

Method for producing viral vector

Disclosed is a cell which can express a non-natural oligomeric protein, which has, introduced therein, a gene encoding an exogenous polypeptide corresponding to at least one endogenous polypeptide constituting a natural oligomeric protein, and in which the expression of the endogenous polypeptide is inhibited.

Method for expression of specific gene

Growing community of inventors

Otsu, Japan

Junichi Mineno