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Pesquisa : A11.284.187.178.190 [Categoria DeCS]
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[PMID]:29065189
[Au] Autor:Satoh D; Iwado S; Abe S; Kazuki K; Wakuri S; Oshimura M; Kazuki Y
[Ad] Endereço:Chromosome Engineering Research Center, Tottori University, Tottori, Japan.
[Ti] Título:Establishment of a novel hepatocyte model that expresses four cytochrome P450 genes stably via mammalian-derived artificial chromosome for pharmacokinetics and toxicity studies.
[So] Source:PLoS One;12(10):e0187072, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The utility of HepG2 cells to assess drug metabolism and toxicity induced by chemical compounds is hampered by their low cytochrome P450 (CYP) activities. To overcome this limitation, we established HepG2 cell lines expressing major CYP enzymes involved in drug metabolism (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and CYP oxidoreductase (POR) using the mammalian-derived artificial chromosome vector. Transchromosomic HepG2 (TC-HepG2) cells expressing four CYPs and POR were used to determine time- and concentration-dependent inhibition and toxicity of several compounds by luminescence detection of CYP-specific substrates and cell viability assays. Gene expression levels of all four CYPs and POR, as well as the CYP activities, were higher in TC-HepG2 clones than in parental HepG2 cells. Additionally, the activity levels of all CYPs were reduced in a concentration-dependent manner by specific CYP inhibitors. Furthermore, preincubation of TC-HepG2 cells with CYP inhibitors known as time-dependent inhibitors (TDI) prior to the addition of CYP-specific substrates determined that CYP inhibition was enhanced in the TDI group than in the non-TDI group. Finally, the IC50 of bioactivable compound aflatoxin B1 was lower in TC-HepG2 cells than in HepG2 cells. In conclusion, the TC-HepG2 cells characterized in the current study are a highly versatile model to evaluate drug-drug interactions and hepatotoxicity in initial screening of candidate drug compounds, which require a high degree of processing capacity and reliability.
[Mh] Termos MeSH primário: Cromossomos Artificiais de Mamíferos
Sistema Enzimático do Citocromo P-450/genética
Inibidores Enzimáticos/farmacologia
Modelos Biológicos
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Inibidores Enzimáticos/farmacocinética
Seres Humanos
Concentração Inibidora 50
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 9035-51-2 (Cytochrome P-450 Enzyme System)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0187072


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[PMID]:28111305
[Au] Autor:Wakuri S; Yamakage K; Kazuki Y; Kazuki K; Oshimura M; Aburatani S; Yasunaga M; Nakajima Y
[Ad] Endereço:Hatano Research Institute, Food and Drug Safety Center, Hadano, Kanagawa 257-8523, Japan.
[Ti] Título:Correlation between luminescence intensity and cytotoxicity in cell-based cytotoxicity assay using luciferase.
[So] Source:Anal Biochem;522:18-29, 2017 Apr 01.
[Is] ISSN:1096-0309
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The luciferase reporter assay has become one of the conventional methods for cytotoxicity evaluation. Typically, the decrease of luminescence expressed by a constitutive promoter is used as an index of cytotoxicity. However, to our knowledge, there have been no reports of the correlation between cytotoxicity and luminescence intensity. In this study, to accurately verify the correlation between them, beetle luciferase was stably expressed in human hepatoma HepG2 cells harboring the multi-integrase mouse artificial chromosome vector. We showed that the cytotoxicity assay using luciferase does not depend on the stability of luciferase protein and the kind of constitutive promoter. Next, HepG2 cells in which green-emitting beetle luciferase was expressed under the control of CAG promoter were exposed to 58 compounds. The luminescence intensity and cytotoxicity curves of cells exposed to 48 compounds showed similar tendencies, whereas those of cells exposed to 10 compounds did not do so, although the curves gradually approached each other with increasing exposure time. Finally, we demonstrated that luciferase expressed under the control of a constitutive promoter can be utilized both as an internal control reporter for normalizing a test reporter and for monitoring cytotoxicity when two kinds of luciferases are simultaneously used in the cytotoxicity assay.
[Mh] Termos MeSH primário: Cromossomos Artificiais de Mamíferos
Proteínas de Insetos
Luciferases
Medições Luminescentes/métodos
Regiões Promotoras Genéticas
[Mh] Termos MeSH secundário: Animais
Cromossomos Artificiais de Mamíferos/genética
Cromossomos Artificiais de Mamíferos/metabolismo
Coleópteros
Células Hep G2
Seres Humanos
Proteínas de Insetos/genética
Proteínas de Insetos/metabolismo
Luciferases/genética
Luciferases/metabolismo
Camundongos
Testes de Toxicidade/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insect Proteins); EC 1.13.12.- (Luciferases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170124
[St] Status:MEDLINE


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[PMID]:26055730
[Au] Autor:Yoshimura Y; Nakamura K; Endo T; Kajitani N; Kazuki K; Kazuki Y; Kugoh H; Oshimura M; Ohbayashi T
[Ad] Endereço:Division of Laboratory Animal Science, Research Center for Bioscience and Technology, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan.
[Ti] Título:Mouse embryonic stem cells with a multi-integrase mouse artificial chromosome for transchromosomic mouse generation.
[So] Source:Transgenic Res;24(4):717-27, 2015 Aug.
[Is] ISSN:1573-9368
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The mouse artificial chromosome (MAC) has several advantages as a gene delivery vector, including stable episomal maintenance of the exogenous genetic material and the ability to carry large and/or multiple gene inserts including their regulatory elements. Previously, a MAC containing multi-integration site (MI-MAC) was generated to facilitate transfer of multiple genes into desired cells. To generate transchromosomic (Tc) mice containing a MI-MAC with genes of interest, the desired genes were inserted into MI-MAC in CHO cells, and then the MI-MAC was transferred to mouse embryonic stem (mES) cells via microcell-mediated chromosome transfer (MMCT). However, the efficiency of MMCT from CHO to mES cells is very low (<10(-6)). In this study, we constructed mES cell lines containing a MI-MAC vector to directly insert a gene of interest into the MI-MAC in mES cells via a simple transfection method for Tc mouse generation. The recombination rate of the GFP gene at each attachment site (FRT, PhiC31attP, R4attP, TP901-1attP and Bxb1attP) on MI-MAC was greater than 50% in MI-MAC mES cells. Chimeric mice with high coat colour chimerism were generated from the MI-MAC mES cell lines and germline transmission from the chimera was observed. As an example for the generation of Tc mice with a desired gene by the MI-MAC mES approach, a Tc mouse strain ubiquitously expressing Emerald luciferase was efficiently established. Thus, the findings suggest that this new Tc strategy employing mES cells and a MI-MAC vector is efficient and useful for animal transgenesis.
[Mh] Termos MeSH primário: Cromossomos Artificiais de Mamíferos/genética
Engenharia Genética/métodos
Vetores Genéticos/genética
Integrases/genética
Células-Tronco Embrionárias Murinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Células CHO
Quimera
Cricetinae
Cricetulus
Citometria de Fluxo
Técnicas de Transferência de Genes
Células Germinativas
Seres Humanos
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos ICR
Camundongos Transgênicos
Células-Tronco Embrionárias Murinas/citologia
Recombinação Genética
Transgenes/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.7.7.- (Integrases)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:150719
[Lr] Data última revisão:
150719
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150610
[St] Status:MEDLINE
[do] DOI:10.1007/s11248-015-9884-6


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[PMID]:25596828
[Au] Autor:Katona RL
[Ad] Endereço:Institute of Genetics, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary, katona.robert@brc.mta.hu.
[Ti] Título:De novo formed satellite DNA-based mammalian artificial chromosomes and their possible applications.
[So] Source:Chromosome Res;23(1):143-57, 2015 Feb.
[Is] ISSN:1573-6849
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Mammalian artificial chromosomes (MACs) are non-integrating, autonomously replicating natural chromosome-based vectors that may carry a vast amount of genetic material, which in turn enable potentially prolonged, safe, and regulated therapeutic transgene expression and render MACs as attractive genetic vectors for "gene replacement" or for controlling differentiation pathways in target cells. Satellite-DNA-based artificial chromosomes (SATACs) can be made by induced de novo chromosome formation in cells of different mammalian and plant species. These artificially generated accessory chromosomes are composed of predictable DNA sequences, and they contain defined genetic information. SATACs have already passed a number of obstacles crucial to their further development as gene therapy vectors, including large-scale purification, transfer of purified artificial chromosomes into different cells and embryos, generation of transgenic animals and germline transmission with purified SATACs, and the tissue-specific expression of a therapeutic gene from an artificial chromosome in the milk of transgenic animals. SATACs could be used in cell therapy protocols. For these methods, the most versatile target cell would be one that was pluripotent and self-renewing to address multiple disease target cell types, thus making multilineage stem cells, such as adult derived early progenitor cells and embryonic stem cells, as attractive universal host cells.
[Mh] Termos MeSH primário: Cromossomos Artificiais de Mamíferos/genética
DNA Satélite/genética
Terapia Genética/métodos
Vetores Genéticos/genética
Mamíferos/genética
Modelos Genéticos
Células-Tronco/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (DNA, Satellite)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150119
[St] Status:MEDLINE
[do] DOI:10.1007/s10577-014-9458-0


  5 / 48 MEDLINE  
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[PMID]:25194736
[Au] Autor:Tóth A; Fodor K; Blazsó P; Cserpán I; Praznovszky T; Tubak V; Udvardy A; Hadlaczky G; Katona RL
[Ad] Endereço:Hungarian Academy of Sciences Institute of Genetics, Biological Research Centre Temesvári krt. 62 H-6726 Szeged Hungary.
[Ti] Título:Generation of induced pluripotent stem cells by using a mammalian artificial chromosome expression system.
[So] Source:Acta Biol Hung;65(3):331-45, 2014 Sep.
[Is] ISSN:0236-5383
[Cp] País de publicação:Hungary
[La] Idioma:eng
[Ab] Resumo:Direct reprogramming of mouse fibroblasts into induced pluripotent stem cells (iPS) was achieved recently by overexpression of four transcription factors encoded by retroviral vectors. Most of the virus vectors, however, may cause insertional mutagenesis in the host genome and may also induce tumor formation. Therefore, it is very important to discover novel and safer, non-viral reprogramming methods. Here we describe the reprogramming of somatic cells into iPS cells by a novel protein-based technique. Engineered Oct4, Sox2 and Klf4 transcription factors carrying an N-terminal Flag-tag and a C-terminal polyarginine tail were synthesized by a recently described mammalian artificial chromosome expression system (ACEs). This system is suitable for the high-level production of recombinant proteins in mammalian tissue culture cells. Recombinant proteins produced in this system contain all the post-translational modifications essential for the stability and the authentic function of the proteins. The engineered Oct4, Sox2 and Klf4 proteins efficiently induced the reprogramming of mouse embryonic fibroblasts by means of protein transduction. This novel method allows for the generation of iPS cells, which may be suitable for therapeutic applications in the future.
[Mh] Termos MeSH primário: Reprogramação Celular
Cromossomos Artificiais de Mamíferos
Fibroblastos/metabolismo
Células-Tronco Pluripotentes/metabolismo
Fatores de Transcrição/metabolismo
Transfecção/métodos
[Mh] Termos MeSH secundário: Animais
Células CHO
Técnicas de Cocultura
Cricetinae
Cricetulus
Regulação da Expressão Gênica no Desenvolvimento
Fatores de Transcrição Kruppel-Like/genética
Fatores de Transcrição Kruppel-Like/metabolismo
Camundongos
Fator 3 de Transcrição de Octâmero/genética
Fator 3 de Transcrição de Octâmero/metabolismo
Fatores de Transcrição SOXB1/genética
Fatores de Transcrição SOXB1/metabolismo
Fatores de Transcrição/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GKLF protein); 0 (Kruppel-Like Transcription Factors); 0 (Octamer Transcription Factor-3); 0 (SOXB1 Transcription Factors); 0 (Transcription Factors)
[Em] Mês de entrada:1410
[Cu] Atualização por classe:141120
[Lr] Data última revisão:
141120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140908
[St] Status:MEDLINE
[do] DOI:10.1556/ABiol.65.2014.3.9


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[PMID]:24454889
[Au] Autor:Tóth A; Fodor K; Praznovszky T; Tubak V; Udvardy A; Hadlaczky G; Katona RL
[Ad] Endereço:Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
[Ti] Título:Novel method to load multiple genes onto a mammalian artificial chromosome.
[So] Source:PLoS One;9(1):e85565, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mammalian artificial chromosomes are natural chromosome-based vectors that may carry a vast amount of genetic material in terms of both size and number. They are reasonably stable and segregate well in both mitosis and meiosis. A platform artificial chromosome expression system (ACEs) was earlier described with multiple loading sites for a modified lambda-integrase enzyme. It has been shown that this ACEs is suitable for high-level industrial protein production and the treatment of a mouse model for a devastating human disorder, Krabbe's disease. ACEs-treated mutant mice carrying a therapeutic gene lived more than four times longer than untreated counterparts. This novel gene therapy method is called combined mammalian artificial chromosome-stem cell therapy. At present, this method suffers from the limitation that a new selection marker gene should be present for each therapeutic gene loaded onto the ACEs. Complex diseases require the cooperative action of several genes for treatment, but only a limited number of selection marker genes are available and there is also a risk of serious side-effects caused by the unwanted expression of these marker genes in mammalian cells, organs and organisms. We describe here a novel method to load multiple genes onto the ACEs by using only two selectable marker genes. These markers may be removed from the ACEs before therapeutic application. This novel technology could revolutionize gene therapeutic applications targeting the treatment of complex disorders and cancers. It could also speed up cell therapy by allowing researchers to engineer a chromosome with a predetermined set of genetic factors to differentiate adult stem cells, embryonic stem cells and induced pluripotent stem (iPS) cells into cell types of therapeutic value. It is also a suitable tool for the investigation of complex biochemical pathways in basic science by producing an ACEs with several genes from a signal transduction pathway of interest.
[Mh] Termos MeSH primário: Cromossomos Artificiais de Mamíferos/genética
Genes
Vetores Genéticos
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Células CHO
Cricetinae
Cricetulus
Primers do DNA
Modelos Animais de Doenças
Hibridização in Situ Fluorescente
Camundongos
Reação em Cadeia da Polimerase
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA Primers)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140124
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0085565


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[PMID]:24216103
[Au] Autor:Kazuki K; Takehara S; Uno N; Imaoka N; Abe S; Takiguchi M; Hiramatsu K; Oshimura M; Kazuki Y
[Ad] Endereço:Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan; Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
[Ti] Título:Highly stable maintenance of a mouse artificial chromosome in human cells and mice.
[So] Source:Biochem Biophys Res Commun;442(1-2):44-50, 2013 Dec 06.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human artificial chromosomes (HACs) and mouse artificial chromosomes (MACs) display several advantages as gene delivery vectors, such as stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Previously, we showed that a MAC vector developed from a natural mouse chromosome by chromosome engineering was more stably maintained in adult tissues and hematopoietic cells in mice than HAC vectors. In this study, to expand the utility for a gene delivery vector in human cells and mice, we investigated the long-term stability of the MACs in cultured human cells and transchromosomic mice. We also investigated the chromosomal copy number-dependent expression of genes on the MACs in mice. The MAC was stably maintained in human HT1080 cells in vitro during long-term culture. The MAC was stably maintained at least to the F8 and F4 generations in ICR and C57BL/6 backgrounds, respectively. The MAC was also stably maintained in hematopoietic cells and tissues derived from old mice. Transchromosomic mice containing two or four copies of the MAC were generated by breeding. The DNA contents were comparable to the copy number of the MACs in each tissue examined, and the expression of the EGFP gene on the MAC was dependent on the chromosomal copy number. Therefore, the MAC vector may be useful not only for gene delivery in mammalian cells but also for animal transgenesis.
[Mh] Termos MeSH primário: Instabilidade Cromossômica
Cromossomos Artificiais de Mamíferos/genética
Técnicas de Transferência de Genes
Vetores Genéticos/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Feminino
Células Germinativas
Seres Humanos
Linfócitos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos ICR
Fatores Sexuais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1404
[Cu] Atualização por classe:131209
[Lr] Data última revisão:
131209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131113
[St] Status:MEDLINE


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[PMID]:22179716
[Au] Autor:Devoy A; Bunton-Stasyshyn RK; Tybulewicz VL; Smith AJ; Fisher EM
[Ad] Endereço:Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
[Ti] Título:Genomically humanized mice: technologies and promises.
[So] Source:Nat Rev Genet;13(1):14-20, 2011 Dec 16.
[Is] ISSN:1471-0064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Mouse models have become an invaluable tool for understanding human health and disease owing to our ability to manipulate the mouse genome exquisitely. Recent progress in genomic analysis has led to an increase in the number and type of disease-causing mutations detected and has also highlighted the importance of non-coding regions. As a result, there is increasing interest in creating 'genomically' humanized mouse models, in which entire human genomic loci are transferred into the mouse genome. The technical challenges towards achieving this aim are large but are starting to be tackled with success.
[Mh] Termos MeSH primário: Cromossomos Artificiais de Mamíferos/genética
Marcação de Genes/métodos
Técnicas de Transferência de Genes
Camundongos Transgênicos/genética
Transgenes/genética
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Doenças Genéticas Inatas/genética
Estudo de Associação Genômica Ampla/métodos
Seres Humanos
Camundongos
Regiões Promotoras Genéticas
Recombinação Genética
Elementos Reguladores de Transcrição
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Em] Mês de entrada:1206
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:111220
[St] Status:MEDLINE
[do] DOI:10.1038/nrg3116


  9 / 48 MEDLINE  
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[PMID]:21431730
[Au] Autor:Kennard ML
[Ad] Endereço:Kennard Biologic Consultants, North Vancouver, BC, Canada. malcolmkennard@shaw.ca
[Ti] Título:Engineered mammalian chromosomes in cellular protein production: future prospects.
[So] Source:Methods Mol Biol;738:217-38, 2011.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The manufacture of recombinant proteins at industrially relevant levels requires technologies that can engineer stable, high expressing cell lines rapidly, reproducibly, and with relative ease. Commonly used methods incorporate transfection of mammalian cell lines with plasmid DNA containing the gene of interest. Identifying stable high expressing transfectants is normally laborious and time consuming. To improve this process, the use of engineered chromosomes has been considered. To date, the most successful technique has been based on the artificial chromosome expression or ACE System, which consists of the targeted transfection of cells containing mammalian based artificial chromosomes with multiple recombination acceptor sites. This ACE System allows for the specific transfection of single or multiple gene copies and eliminates the need for random integration into native host chromosomes. The utility of using artificial engineered mammalian chromosomes, specifically the ACE System, is illustrated in several case studies covering the generation of CHO cell lines expressing monoclonal antibodies.
[Mh] Termos MeSH primário: Cromossomos Artificiais de Mamíferos/genética
Engenharia Genética/métodos
Biossíntese de Proteínas/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Seres Humanos
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/genética
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Recombinant Proteins)
[Em] Mês de entrada:1107
[Cu] Atualização por classe:110324
[Lr] Data última revisão:
110324
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110325
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-61779-099-7_15


  10 / 48 MEDLINE  
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[PMID]:21431729
[Au] Autor:Katona RL; Vanderbyl SL; Perez CF
[Ad] Endereço:Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary. katona@brc.hu
[Ti] Título:Mammalian artificial chromosomes and clinical applications for genetic modification of stem cells: an overview.
[So] Source:Methods Mol Biol;738:199-216, 2011.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Modifying multipotent, self-renewing human stem cells with mammalian artificial chromosomes (MACs), present a promising clinical strategy for numerous diseases, especially ex vivo cell therapies that can benefit from constitutive or overexpression of therapeutic gene(s). MACs are nonintegrating, autonomously replicating, with the capacity to carry large cDNA or genomic sequences, which in turn enable potentially prolonged, safe, and regulated therapeutic transgene expression, and render MACs as attractive genetic vectors for "gene replacement" or for controlling differentiation pathways in progenitor cells. The status quo is that the most versatile target cell would be one that was pluripotent and self-renewing to address multiple disease target cell types, thus making multilineage stem cells, such as adult derived early progenitor cells and embryonic stem cells, as attractive universal host cells. We will describe the progress of MAC technologies, the subsequent modifications of stem cells, and discuss the establishment of MAC platform stem cell lines to facilitate proof-of-principle studies and preclinical development.
[Mh] Termos MeSH primário: Terapia Baseada em Transplante de Células e Tecidos/métodos
Cromossomos Artificiais de Mamíferos/genética
Engenharia Genética/métodos
Células-Tronco/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Linhagem Celular
Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos
Instabilidade Cromossômica
Seres Humanos
Células-Tronco/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1107
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110325
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-61779-099-7_14



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