JP2021525548A - 転写調節エレメント及びそれの外来タンパク質発現の増強における応用 - Google Patents
転写調節エレメント及びそれの外来タンパク質発現の増強における応用 Download PDFInfo
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Abstract
Description
(i)SEQ ID NO:3-9のいずれかで示される配列を含むヌクレオチド配列;
(ii)SEQ ID NO:3-9のいずれかで示される配列の逆相補配列を含むヌクレオチド配列;
(iii)高ストリンジェントなハイブリダイゼーション条件下またはより高ストリンジェントなハイブリダイゼーション条件下で、(i)または(ii)で示されるヌクレオチド配列とハイブリダイズ可能な配列の逆相補配列;
(iv)(i)または(ii)で示されるヌクレオチド配列に対して、少なくとも90%、さらに少なくとも95%、好ましくは少なくとも97%、より好ましくは少なくとも98%、最も好ましくは少なくとも99%の配列同一性を有する配列;
である、ポリヌクレオチド。
(v)SEQ ID NO:13で示される配列を含むヌクレオチド配列;
(vi)SEQ ID NO:13で示される配列の逆相補配列を含むヌクレオチド配列;
(vii)高ストリンジェントなハイブリダイゼーション条件下またはより高ストリンジェントなハイブリダイゼーション条件下で、(v)または(vi)で示されるヌクレオチド配列とハイブリダイズ可能な配列の逆相補配列;
(viii)(v)または(vi)で示されるヌクレオチド配列に対して、少なくとも90%、さらに少なくとも95%、好ましくは少なくとも97%、より好ましくは少なくとも98%、最も好ましくは少なくとも99%の配列同一性を有する配列;
である、(1)に記載のポリヌクレオチド。
(i)前記分泌されたタンパク質が前記検出標的タンパク質と相互作用できた場合、前記動物患が疾患を持っていることを示す;
(ii)前記分泌されたタンパク質が前記検出標的タンパク質と相互作用できない場合、前記動物が疾患を持っていないことを示す。
(i)(14)に記載のタンパク質を製造する方法に従って、前記タンパク質を製造して得られる;
(ii)ステップ(i)で得られた前記タンパク質を動物に免疫させて、対応する前記標的抗体を得る、
方法。
任意に、本発明は以下の実施形態を提供する。
(36)以下の配列を含む、抗体の発現を増強するための宿主細胞であって、
SEQ ID NO:3-9のいずれかの配列と少なくとも85%の同一性を有する配列またはSEQ ID NO:3-9のいずれかの配列の逆相補配列に作動可能に連結されている、抗体軽鎖またはその断片をコードする第2のポリヌクレオチド;
である、宿主細胞。
本開示の特許請求の範囲および/または明細書において、「一(a)」または「一(an)」または「一(the)」という単語は「1つ」を指す場合があるが、「1つまたは複数」、「少なくとも1つの」及び「1つまたは1つ超」 を指すことができる。
実施例
転写調節エレメントBの配列は、SEQ ID NO:4で示される配列(SEQ ID NO: 4の逆相補配列はSEQ ID NO: 18)であった;
転写調節エレメントCの配列は、SEQ ID NO:5で示される配列(SEQ ID NO: 5の逆相補配列はSEQ ID NO: 19)であった;
転写調節エレメントDの配列は、SEQ ID NO:6で示される配列(SEQ ID NO: 6の逆相補配列はSEQ ID NO: 20)であった;
転写調節エレメントEの配列は、SEQ ID NO:7で示される配列(SEQ ID NO: 7の逆相補配列はSEQ ID NO: 21)であった;
転写調節エレメントFの配列は、SEQ ID NO:8で示される配列(SEQ ID NO: 8の逆相補配列はSEQ ID NO: 22)であった;
転写調節エレメントGの配列は、SEQ ID NO:9で示される配列(SEQ ID NO: 9の逆相補配列はSEQ ID NO: 23)であった。
前述ベクターは、例えばPvuI(NEB)などの酵素消化部位がベクターバックボーンの原核領域のみにある制限エンドヌクレアーゼを使用して線形化され、37℃で一晩保存した。翌日にフェノール‐クロロホルム法によりDNAを回収してトランスフェクトに用いた。
Claims (20)
- (i)〜(iv)からなる群から選択されるヌクレオチド配列を含むポリヌクレオチド分子であって:
(i)SEQ ID NO:3-9のいずれかの配列;
(ii)SEQ ID NO:3-9のいずれかの配列の逆相補配列;
(iii)高ストリンジェントなハイブリダイゼーション条件下またはより高ストリンジェントなハイブリダイゼーション条件下で、(i)または(ii)の配列とハイブリダイズ可能な配列の逆相補配列;及び
(iv)(i)または(ii)の配列に対して、少なくとも80%、または少なくとも90%、さらに少なくとも95%、好ましくは少なくとも97%、より好ましくは少なくとも98%、最も好ましくは少なくとも99%の配列同一性を有する配列;
である、単離されたポリヌクレオチド分子。 - 請求項1に記載のポリヌクレオチド分子を含むベクター。
- 前記ベクターが組換え発現ベクターである請求項2に記載のベクター。
- (v)〜(viii)からなる群から選択されるヌクレオチド配列をさらに含む、
(v)SEQ ID NO:13の配列;
(vi)SEQ ID NO:13の配列の逆相補配列;
(vii)高ストリンジェントなハイブリダイゼーション条件下またはより高ストリンジェントなハイブリダイゼーション条件下で、(v)または(vi)の配列とハイブリダイズ可能な配列の逆相補配列;及び
(viii)(v)または(vi)の配列に対して、少なくとも80%、または少なくとも90%、さらに少なくとも95%、好ましくは少なくとも97%、より好ましくは少なくとも98%、最も好ましくは少なくとも99%の配列同一性を有する配列;
である、請求項2または3に記載のベクター。 - CMVプロモーターをさらに含み、好ましくは、前記CMVプロモーターはSEQ ID NO:16のヌクレオチド配列を含むか、または前記CMVプロモーターは、前記SEQ ID NO:16の配列に対して少なくとも80%、または少なくとも90%、さらに少なくとも95%、好ましくは少なくとも97%、より好ましくは少なくとも98%、最も好ましくは少なくとも99%の配列同一性を有する配列を含む、請求項2〜4のいずれか一項に記載のベクター。
- 以下の組み合わせを含む:
(1)SEQ ID NO:4の配列または該配列に対して90%の同一性を有する配列;
(2)SEQ ID NO:13の配列または該配列に対して90%の同一性を有する配列;及び
(3)SEQ ID NO:16の配列または該配列に対して90%の同一性を有する配列;
である、請求項5に記載のベクター。 - 一種類または多種類のタンパク質をコードする1つ以上の遺伝子をさらに含む請求項2〜6のいずれか一項に記載のベクター。
- 前記タンパク質は、抗体、融合タンパク質、酵素、可溶性タンパク質、膜タンパク質、構造タンパク質、リボソームタンパク質、チモーゲン、細胞表面受容体タンパク質、転写調節タンパク質、翻訳調節タンパク質、クロマチンタンパク質、ホルモン、細胞周期調節タンパク質、Gタンパク質、神経活性化ペプチド、免疫調節タンパク質、血液成分タンパク質、イオンチャネルタンパク質、熱ショックタンパク質、ジヒドロ葉酸レダクターゼ、抗生物質耐性タンパク質、いずれかの前記タンパク質の機能的フラグメント、いずれかの前記タンパク質のエピトープフラグメント、ならびにそれらの任意の組み合わせからなる群から選択される、請求項7に記載のベクター。
- 請求項2〜8のいずれか一項に記載のベクターを含む組換え宿主細胞。
- タンパク質を安定的に発現する組換え宿主細胞を製造する方法であって、請求項2〜8のいずれか一項に記載のベクターを宿主細胞に挿入するステップを含む方法。
- 前記宿主細胞がチャイニーズハムスター卵巣(CHO)細胞である請求項9に記載の組換え宿主細胞または請求項10に記載の方法。
- タンパク質を製造する方法であって、タンパク質の産生を可能にする条件下で、請求項9または11に記載の組換え宿主細胞を培養するステップを含む方法。
- 請求項9または11に記載の組換え宿主細胞を含むキット。
- 異常なタンパク質発現による疾患を検出するための試薬またはキットの製造における、請求項9または11に記載の組換え宿主細胞の使用。
- 疾患を治療または予防するための医薬品の製造における、請求項9または11に記載の組換え宿主細胞の使用。
- タンパク質を安定的に発現する組換え宿主細胞をスクリーニングする方法であって、ブラスチシジンとゼオシンを含む選択培地を用いて宿主細胞をスクリーニングするステップを含む方法。
- ブラスチシジンが1-15μg/mLの量で存在し、ゼオシンが50-1500μg/mLの量で存在する請求項16に記載の方法。
- ブラスチシジンが4-9μg/mLの量で存在し、ゼオシンが200-400μg/mLの量で存在する請求項17に記載の方法。
- ブラスチシジンが9μg/mLの量で存在し、ゼオシンが400μg/mLの量で存在する請求項18に記載の方法。
- ブラスチシジンが4μg/mLの量で存在し、ゼオシンが200μg/mLの量で存在する請求項18に記載の方法。
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JP2008529510A (ja) * | 2005-02-11 | 2008-08-07 | クアトロメッド セル ファクトリー オーユー | ハイブリッドプラスミドの延長されたエピソーム維持複製および遺伝子産物発現を得るためのベクター、細胞株およびそれらの使用 |
US20160159926A1 (en) * | 2014-12-05 | 2016-06-09 | Samsung Bioepis Co., Ltd. | Fusion polynucleotide containing murine cmv promoter and method of preparing a polypeptide of interest using the same |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
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JP4407635B2 (ja) | 2003-07-22 | 2010-02-03 | 株式会社大真空 | 音叉型振動片、音叉型振動子、および音叉型振動片の製造方法 |
US8377653B2 (en) * | 2005-02-11 | 2013-02-19 | Icosagen Cell Factory Oü | Viral expression plasmids for production of proteins, antibodies, enzymes, virus-like particles and for use in cell-based assays |
US20080124760A1 (en) * | 2006-07-26 | 2008-05-29 | Barbara Enenkel | Regulatory Nucleic Acid Elements |
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CN105821078A (zh) * | 2010-12-09 | 2016-08-03 | 巴斯德研究所 | 用于获得高产量重组蛋白表达的基于mgmt的方法 |
EP2711426B1 (en) * | 2012-09-24 | 2015-04-08 | Lonza Biologics plc | Expression vectors comprising chimeric cytomegalovirus promoter and enhancer sequences |
CN103834686B (zh) * | 2012-11-23 | 2016-05-25 | 上海药明生物技术有限公司 | 高效克隆筛选表达载体、其制备方法及用途 |
KR101599138B1 (ko) | 2014-06-17 | 2016-03-03 | 한국생명공학연구원 | 재조합 단백질 발현 증진을 위한 유전자 절편을 포함하는 벡터 및 이의 용도 |
CN106459999A (zh) * | 2014-06-18 | 2017-02-22 | 新加坡科技研究局 | 用于高水平表达的新型启动子 |
CN106432501B (zh) * | 2015-08-06 | 2021-07-30 | 基石药业 | 新型抗pd-l1抗体 |
CN105255895B (zh) * | 2015-11-06 | 2018-01-02 | 爱博环球生物技术有限公司 | 用于真核细胞系的提高蛋白表达水平的mar转录调控元件及其表达系统 |
US11530277B2 (en) * | 2016-04-20 | 2022-12-20 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for making antibodies based on use of an expression-enhancing locus |
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US20160159926A1 (en) * | 2014-12-05 | 2016-06-09 | Samsung Bioepis Co., Ltd. | Fusion polynucleotide containing murine cmv promoter and method of preparing a polypeptide of interest using the same |
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US11254952B2 (en) | 2022-02-22 |
WO2020034986A1 (en) | 2020-02-20 |
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US20210254100A1 (en) | 2021-08-19 |
CN116555264A (zh) | 2023-08-08 |
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CN113039272B (zh) | 2023-05-30 |
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