Other

Sumitomo Pharmaceuticals Company Limited

Dainippon Sumitomo Pharma Co., Ltd.

National Institute of Health

Japan As Represented by Director General of Agency of National Institute

Tokyo Metropolitan Institute of Medical Science

Izumu Saito

Japan As Represented by the Director General of the Agency of National

Japan As Represented by Director General of the Agency of the National

Japan As Respresented by the Director General of the Agency of National

Saito, Izumu

Tatsuo Miyamura

Yoshiharu Matsuura

Shizuko Harada

Yoshikazu Honda

Yumi Saito

Makoto Seki

Yumi Kanegae

Michio Nakai

Joe Chiba

Takaji Wakita

Michinori Kohara

Hiromichi Yonekawa

Naoki Tohdoh

Choji Taya

Kazuo Komiya

Masashi Murata

Keiji Tanaka

The present invention provides a novel adenovirus vector for which inflammation during the in vivo administration thereof is alleviated by inhibiting the induction of expression of an adenovirus gene by a foreign promoter inserted into the adenovirus genome, and a method for producing the vector, a cell line for use in the production of the recombinant adenovirus vector, or a gene therapy method using the recombinant adenovirus vector.

Recombinant adenovirus vector having a reduced side effect

A novel cosmid vector and the like effectively used in generating a recombinant adenoviral vector are provided. More specifically, there are provided a cosmid vector characterized by:

Cosmid vector

To provide DNA comprising mutant FRT sequence which causes recombination reaction between two mutant FRT sequences having an identical sequence to each other but does not cause recombination reaction with a wild-type FRT sequence, in the presence of FLP recombinase; and a method for performing high-efficiency, gene insertion or gene replacement. A DNA comprising a mutant FRT sequence (any one of SEQ ID NOs: 2 to 5); a DNA comprising a mutant FRT sequence possessing (A) causing no specific DNA recombination reaction with wild type FRT, even if FLP recombinase is present, and (B) causing specific DNA recombination reaction with another mutant FRT sequence having an identical sequence thereto in the presence of recombinase FLP, wherein the mutant FRT sequence has substitutions of at least one nucleotide in a region other than the spacer region in the sequence and a cell which is transformed with the DNA.

DNA containing variant FRT sequences

To provide DNA comprising mutant FRT sequence which causes recombination reaction between two mutant FRT sequences having an identical sequence to each other but does not cause recombination reaction with a wild-type FRT sequence, in the presence of FLP recombinase; and a method for performing high-efficiency, gene insertion or gene replacement. A DNA comprising a mutant FRT sequence. A DNA comprising a mutant FRT sequence possessing (A) causing no specific DNA recombination reaction with wild type FRT, even if FLP recombinase is present, and (B) causing specific DNA recombination reaction with another mutant FRT sequence having an identical sequence thereto in the presence of recombinase FLP; gene replacement method using the DNA in the presence of recombinase FLP; and a specific DNA recombination method, characterized in that a specific DNA recombination reaction is carried out by using two mutant FRT sequences in the presence of recombinase FLP.

Recombinant adenoviruses comprising the following sequences in the genome: (1) a left inverted terminal repeat: (2) a packaging signal: (3) a recombinase recognition sequence located at a region in between said left inverted terminal repeat and said packaging signal: and (4) at least one more recombinase recognition sequence which is located downstream of said packaging signal and which is recognized by the recombinase that recognizes the above recombinase recognition sequence are useful as a material for constructing highly safe vectors for gene therapy in the field of gene therapy.

Recombinant adenovirus

Mutant loxP site and applications thereof

A hepatitis type C animal model into which cDNA derived from hepatitis C virus has been introduced. This animal model is useful for clarification of an onset mechanism of hepatitis C and as well as for development of means for treating the disease.

Hepatitis C animal model

Transgenic mice are described which serve as a model for Hepatitis C infection. The transgenic mice contain, in their germline and somatic cells, the Hepatitis C viral fragment CN2, N24 or CR under the control of a Cre-loxP switch-expression system. Administration of Cre to the mice results in a phenotype of increased serum GTP levels, emergence of acidophilic bodies in the liver, exfoliation of hepatic cells, hypertrophy and hyperplasia of Kupffer's cells, and conglomeration of lymphocytes.

Transgenic mouse hepatitis C virus model comprising a hepatitis C viral fragment

A method for extracellularly producing an ectoprotein of hepatitis C virus comprises the steps of cultivating a transformant which is transformed with an expression vector containing a DNA fragment coding for the ectoprotein of hepatitis C virus and recovering the ectoprotein of hepatitis C virus extracellularly produced by the transformant. The protein originated from the E1 region prepared by the method can be used as a material for preparing a vaccine for preventing HCV infection. In addition, a diagnostic agent containing the protein is useful for the detection of an HCV antibody or the confirmation of the presence thereof in sera or the like. In other words, the protein of the present invention permits the diagnosis of C type hepatitis in high specificity and sensitivity.

Method for producing ectoprotein of hepatitis C virus

Method of producing ectoprotein of hepatitis C virus

An animal cell is co-transfected with both a recombinant DNA viral vector which bears a promoter, a recombinase gene and a poly(A) sequence and a recombinant DNA viral vector which bears two recombinase-recognizing sequences and which further bears an origin of replication, a promoter, a foreign gene and a poly(A) sequence, each of which is located between the two recombinase-recognizing sequences. Thereafter, in the co-transfected animal cell, a DNA fragment containing the origin of replication, promoter, foreign gene and poly(A) sequence is excised from the vector by the action of a recombinase expressed in the another vector. The DNA fragment forms a circular DNA molecule which autonomously replicates in the co-transfected animal cell due to the origin of replication, whereby the foreign gene is continuously expressed. Accordingly, the combination of the above two DNA viral vectors wherein a gene which is defective in patients is used as the foreign gene is quite useful especially for the treatment of the patient with hereditary diseases.

Recombinant DNA viral vector for transfecting animal cells

A diagnostic reagent for hepatitis C, which detects an antibody induced by infection of hepatitis C virus, and comprises the second envelope protein or first non-structural protein which is encoded by the gene of hepatitis C virus and has a sugar chain. This invention also provide a method for detecting an anti-hepatitis C virus antibody. The use of the diagnostic reagent for hepatitis C according to the present invention makes highly sensitive diagnosis of hepatitis C possible.

Diagnostic reagent for hepatitis C

A diagnostic reagent for hepatitis C, which detects an antibody induced by infection of hepatitis C virus, comprising the second envelope protein or first non-structural protein which is encoded by the gene of hepatitis C virus and has a sugar chain. This invention also provides a method for detecting an anti-hepatitis C virus antibody. The use of the diagnostic reagent for hepatitis C according to the present invention makes highly sensitive diagnosis of hepatitis C possible.

Growing community of inventors

Tokyo, Japan

Izumu Saito