Abstract: The following are provided: a novel adenovirus vector having a shortened backbone; a nucleic acid vector expressing five or more Cas guide RNA; a nucleic acid vector containing a Cas protein-coding gene and a Cas guide RNA expression unit; a composition for genome editing containing these vectors; and a gene therapeutic method using these.

Abstract: 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.

Abstract: 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: (1) containing an adenoviral genome having adenoviral inverted terminal repeat sequences each having a complete nucleotide sequence, (2) having a deletion in an adenovirus E1 gene region, and (3) containing a restriction enzyme recognition sequence not present in the adenoviral genome, on both sides of the adenoviral genome; a method of generating a recombinant adenoviral vector using the cosmid vector; and a reagent for generating a recombinant adenoviral vector containing the cosmid vector as a component.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: In accordance with the present invention, there are provided cells for expressing recombinase Cre in the presence of recombinase FLP in a FLP-dependent manner, methods of expressing recombinase Cre by introducing recombinase FLP into the above cells, methods of producing recombinant viral vectors using cells that express recombinase Cre in the presence of recombinase FLP in a FLP-dependent manner, and methods of producing recombinant adenovirus vectors using the above method of producing Cre and the above method of producing recombinant viral vectors.

Abstract: 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.

Abstract: 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: (1) containing an adenoviral genome having adenoviral inverted terminal repeat sequences each having a complete nucleotide sequence, (2) having a deletion in an adenovirus E1 gene region, and (3) containing a restriction enzyme recognition sequence not present in the adenoviral genome, on both sides of the adenoviral genome; a method of generating a recombinant adenoviral vector using the cosmid vector; and a reagent for generating a recombinant adenoviral vector containing the cosmid vector as a component.

Abstract: 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.

Abstract: 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.

Abstract: In accordance with the present invention, there are provided cells for expressing recombinase Cre in the presence of recombinase FLP in a FLP-dependent manner, methods of expressing recombinase Cre by introducing recombinase FLP into the above cells, methods of producing recombinant viral vectors using cells that express recombinase Cre in the presence of recombinase FLP in a FLP-dependent manner, and methods of producing recombinant adenovirus vectors using the above method of producing Cre and the above method of producing recombinant viral vectors.

Abstract: 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.

Abstract: 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 said recombinant adenovirus vector, or a gene therapy method using said recombinant adenovirus vector.

Abstract: Highly efficient gene integration or gene replacement in the higher eucaryote including animal cells can be performed by using mutant loxP site having the following properties (a)-(c) in the present invention. (a) a nucleotide sequence wherein, in a wild-type loxP site of the following formula (SEQ ID NO: 1) derived from E.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.