Growth control of genetically modified cells using an antibody/c-Kit chimera(CELL AND TISSUE ENGINEERING)
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概要
- 論文の詳細を見る
Gene therapy has been regarded as an innovative potential treatment against serious congenital diseases. However, applications of gene therapy remain limited, partly because its clinical success depends on therapeutic gene-transduced cells acquiring a proliferative advantage. To address this problem, we have developed the antigen-mediated genetically modified cell amplification (AMEGA) system, which uses chimeric receptors to enable the selective proliferation of gene-transduced cells. In this report, we describe mimicry of c-Kit signaling and its application to the AMEGA system. We created an antibody/c-Kit chimera in which the extracellular domain of c-Kit is replaced with an anti-fluorescein single-chain Fv antibody fragment and the extracellular D2 domain of the erythropoietin receptor. A genetically modified mouse pro-B cell line carrying this chimera showed selective expansion in the presence of fluorescein-conjugated BSA (BSA-FL) as a growth inducer. By further engineering the transmembrane domain of the chimera to reduce interchain interaction we attained stricter ligand-dependency. Since c-Kit is an important molecule in the expansion of hematopoietic stem cells (HSCs), this antibody/c-Kit chimera could be a promising tool for gene therapy targeting HSCs.
- 公益社団法人日本生物工学会の論文
著者
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上田 宏
東大院・工・化生:東大院・工・バイオエンジ
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上田 宏
東京大学大学院工学系研究科化学生命工学専攻
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Nagamune T
Univ. Tokyo Tokyo Jpn
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Nagamune T
Department Of Chemistry And Biotechnology School Of Engineering The University Of Tokyo
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Nagamune Teruyuki
Dep. Of Chemistry And Biotechnology Graduate School Of Engineering The Univ. Of Tokyo 7-3-1 Hongo Bu
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Nagamune Teruyuki
Department Of Bioengineering Graduate School Of Engineering The University Of Tokyo:department Of Ch
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Nagamune Teruyuki
Department Of Bioengineering Center For Nanobio Integration The University Of Tokyo:department Of Ch
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上田 宏
東京大学大学院工学研究科
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Kawahara Masahiro
Department Of Chemistry And Biotechnology School Of Engineering
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Kawahara Masahiro
Department Of Analytical Chemistry Faculty Of Pharmaceutical Sciences The University Of Tokyo
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Nagamune Teruyuki
Department Of Chemistry And Biotechnology Graduate School Of Engineering The University Of Tokyo:dep
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Kaneko Etsuji
Department Of Chemistry And Biotechnology School Of Engineering The University Of Tokyo
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Ueda Hiroshi
Department Of Anatomy School Of Medicine University Of Occupational And Environmental Health
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Kawahara Masahiro
Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo
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