JP2000501281A - 条件複製起点をもつ環状dna分子、それらの製造方法、及び、遺伝子治療におけるそれらの使用 - Google Patents
条件複製起点をもつ環状dna分子、それらの製造方法、及び、遺伝子治療におけるそれらの使用Info
- Publication number
- JP2000501281A JP2000501281A JP9511716A JP51171697A JP2000501281A JP 2000501281 A JP2000501281 A JP 2000501281A JP 9511716 A JP9511716 A JP 9511716A JP 51171697 A JP51171697 A JP 51171697A JP 2000501281 A JP2000501281 A JP 2000501281A
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- Prior art keywords
- replication
- dna molecule
- protein
- plasmid
- gene
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.少なくとも1つの有益な核酸配列を含み、前記核酸配列の複製を可能にする 領域がプラスミドまたはバクテリオファージに由来の複製起点を含み、前記複製 起点が宿主細胞中で機能するためには前記宿主細胞に外来の少なくとも1つの特 異的タンパク質の存在が必要であることを特徴とする遺伝子治療に有用な環状D NA分子。 2.条件複製起点が、複数の反復配列によって表される複製起点を有しており且 つその複製起点の機能を左右する少なくとも1つの特異的タンパク質をコードし ているプラスミドまたはバクテリオファージに由来することを特徴とする請求項 1に記載のDNA分子。 3.条件複製起点が、RK2、R6K、R1、pSC101、Rts1、F、R SF1010、P1、P4、ラムダ、ファイ82及びファイ80のようなプラス ミドまたはバクテリオファージに由来し得ることを特徴とする請求項1または2 に記載のDNA分子。 4.前記複製起点が、細菌プラスミドR6Kに由来することを 特徴とする請求項1から3のいずれか一項に記載のDNA分子。 5.前記複製起点が、プラスミドR6Kのγ複製起点の全部または一部から成る ことを特徴とする請求項1から4のいずれか一項に記載のDNA分子。 6.前記複製起点の全部または一部が配列番号1の配列またはその誘導体の1つ の配列によって表されることを特徴とする請求項1から5のいずれか一項に記載 のDNA分子。 7.前記DNA分子を取込んだ宿主細胞を選択し得る領域が、抗生物質耐性遺伝 子とは異なっていることを特徴とする請求項1から6のいずれか一項に記載のD NA分子。 8.前記DNA分子を取込んだ宿主細胞を選択し得る領域の全部または一部が、 特異的コドンのサプレッサー転移RNAの発現カセットによって表されることを 特徴とする請求項1から7のいずれか一項に記載のDNA分子。 9.前記発現カセットが、アンバーコドン(TAG)のサプレッサーtRNAの 発現カセットであることを特徴とする請求項8に記載のDNA分子。 10.更に、部位特異的リコンビナーゼの標的領域を含むことを特徴とする請求 項1から9のいずれか一項に記載のDNA分 子。 11.部位特異的リコンビナーゼの前記標的領域が、トランスポゾンTn3、T n21またはTn522のリゾルベース、ミューバクテリオファージのインベル ターゼ、RP4のparフラグメントによってコードされているリゾルベースの ようなプラスミドのリゾルベース、ラムダ、ファイ80、P22、HP1のイン テグラーゼのようなラムダバクテリオファージのインテグラーゼのファミリーの リコンビナーゼ、P1のCreインテグラーゼ、プラスミドpSAM2のインテ グラーゼ、プラスミド2μのFLPリコンビナーゼ、大腸菌のリコンビナーゼX erC及びXerDから選択され得ることを特徴とする請求項10に記載のDN A分子。 12.部位特異的リコンビナーゼの前記標的領域が、ColE1またはその誘導 体の1つのcerフラグメントの全部または一部を含むことを特徴とする請求項 10または11に記載のDNA分子。 13.プラスミドpXL2774またはその誘導体の1つから成ることを特徴と する請求項1から12のいずれか一項に記載のDNA分子。 14.有益な核酸配列が、薬品製造、農業生産または生体触媒作用に使用できる 有益なタンパク質をコードしていることを特徴とする請求項1から13のいずれ か一項に記載のDNA分子。 15.有益な核酸配列が、酵素;血液誘導体;ホルモン;インターロイキン、イ ンターフェロン、TNFなどのリンフォカイン;成長因子;神経伝達物質または その前駆体またはその合成用酵素;BDNF、CNTF、NGF、IGF、GM F、aFGF、bFGF、NT3、NT5のような栄養因子;ApoAI、Ap oAIV、ApoEのようなアポリポタンパク質;ジストロフィンまたはミニジ ストロフィン;p53、Rb、Rap1A、DCC、k−revのような腫瘍抑 制遺伝子;VII因子、VIII因子、IX因子のような凝固に関与する因子を コードする遺伝子;チミジンキナーゼ、シトシンデザミナーゼのような自殺遺伝 子;Fab、ScFvのような天然または人工の免疫グロブリンの全部または一 部;RNAリガンド;アンチセンス配列;エプスタイン・バールウイルス、HI Vウイルス、肝炎Bウイルス、偽狂犬病ウイルス特異的または腫瘍特異的な抗原 性ペプチド、から選択されたタンパク質をコードしていることを特徴とする請求 項14に記載のDNA分子。 16.−少なくとも1つの有益な核酸配列と前記核酸配列の複製を可能にする領 域とを含み、前記領域が複製起点を含んでおり、前記複製起点が宿主細胞中で機 能するためには前記宿主細胞に外来の少なくとも1つの特異的タンパク質の存在 が必要である環状DNA分子と、 −in situ発現するか否かによって、前記宿主細胞に外来の特異的複製 起点の機能を左右するタンパク質、 とを少なくとも含む宿主細胞を、前記DNA分子によって形質転換された宿主細 胞が選択され得る条件下で培養することを特徴とする環状DNA分子の製造方法 。 17.複製開始タンパク質をコードする遺伝子が追加レプリコン上に存在するか または前記細胞のゲノムに取込まれていることを特徴とする請求項16に記載の 方法。 18.請求項4から6のいずれか一項に記載の複製起点を取込んだDNA分子で あること、及び、前記タンパク質がプラスミドR6Kのπタンパク質であるかま たはその誘導体であることを特徴とする請求項16または17に記載の方法。 19.πタンパク質またはその誘導体の1つが、宿主細胞中に存在する配列2で 表されるpir遺伝子またはその誘導体の1 つからin situ発現されることを特徴とする請求項18に記載の方法。 20.タンパク質が前記細胞のゲノムに取込まれたpir116遺伝子から発現 されることを特徴とする請求項19に記載の方法。 21.選択された培養条件で宿主細胞の必須遺伝子の1つが、選択されたサプレ ッサーtRNAによって認識可能な特異的コドンをDNA分子の処に含んでいる ことを特徴とする請求項16から20のいずれか一項に記載の方法。 22.前記遺伝子がアンバーコドンTAGを含むことを特徴とする請求項21に 記載の方法。 23.細胞が大腸菌の菌株から選択されることを特徴とする請求項16から22 のいずれか一項に記載の方法。 24.細胞が大腸菌XAC−1株に由来することを特徴とする請求項16から2 3のいずれか一項に記載の方法。 25.pir116遺伝子をそのゲノムに組込んでおりプラスミドpXL277 4またはその誘導体の1つによって形質転換された大腸菌XAC−1株を使用す ることを特徴とする請求項16から24のいずれか一項に記載の方法。 26.請求項1から15のいずれか一項に記載されているかまたは請求項16か ら25のいずれか一項に記載の方法で製造された少なくとも1つのDNA分子に よって形質転換された組換え細胞。 27.請求項1から15のいずれか一項に記載の1つまたは複数のDNA分子を 含む医薬組成物。 28.有益な遺伝子を宿主細胞にin vitro、exvivo及び/または in vivoでトランスフェクションするための請求項1から15のいずれか 一項に記載のDNA分子の使用。 29.組換えタンパク質をin vitro産生するための請求項1から15の いずれか一項に記載のDNA分子の使用。 30.−組換えタンパク質をコードする少なくとも1つの核酸配列と前記核酸配 列の複製を可能にする領域とを含み、前記領域が複製起点を含み、前記複製起点 が宿主細胞中で機能するためには前記宿主細胞に外来の少なくとも1つの特異的 タンパク質の存在が必要である環状DNA分子と、 −in situ発現するか否かによって、前記宿主細胞に外来の特異的複製 起点の機能を左右するイニシエータータンパ ク質、とを少なくとも含む宿主細胞を培養し、次いで、産生された組換えタンパ ク質を回収することを特徴とする組換えタンパク質の製造方法。 31.複製開始タンパク質をコードする遺伝子が追加レプリコン上に存在するか または前記細胞のゲノムに取込まれていることを特徴とする請求項30に記載の 方法。 32.細胞が大腸菌の菌株から選択されることを特徴とする請求項30または3 1に記載の方法。 33.有益な核酸配列が野生型または修飾されたp53タンパク質をコードして いることを特徴とする請求項1に記載の分子。 34.有益な核酸配列がチミジンキナーゼをコードしていることを特徴とする請 求項1に記載の分子。 35.細胞が大腸菌endA1−株であることを特徴とする請求項23に記載の 方法。 36.更に、リガンドと特異的に相互作用し得る配列を含むことを特徴とする請 求項1から15のいずれか一項に記載のDNA分子。 37.有益な核酸がp53タンパク質をコードしていることを特徴とする請求項 15に記載のDNA分子。
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FR95/10825 | 1995-09-15 | ||
FR9510825A FR2738842B1 (fr) | 1995-09-15 | 1995-09-15 | Molecule d'adn circulaire a origine de replication conditionnelle, leur procede de preparation et leur utilisation en therapie genique |
PCT/FR1996/001414 WO1997010343A1 (fr) | 1995-09-15 | 1996-09-13 | Molecule d'adn circulaire a origine de replication conditionnelle, leur procede de preparation et leur utilisation en therapie genique |
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JP2007205143A Expired - Fee Related JP4756014B2 (ja) | 1995-09-15 | 2007-08-07 | 条件複製起点をもつ環状dna分子、それらの製造方法、及び、遺伝子治療におけるそれらの使用 |
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JP2007205143A Expired - Fee Related JP4756014B2 (ja) | 1995-09-15 | 2007-08-07 | 条件複製起点をもつ環状dna分子、それらの製造方法、及び、遺伝子治療におけるそれらの使用 |
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EP (3) | EP1724354B1 (ja) |
JP (3) | JP3818665B2 (ja) |
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HU (1) | HU224400B1 (ja) |
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TW (1) | TWI231826B (ja) |
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JP2006502714A (ja) * | 2002-10-11 | 2006-01-26 | サントリオン | 条件複製起点をもつ環状dna分子、それらの製造方法、及び、遺伝子治療におけるそれらの使用 |
JP2009509544A (ja) * | 2005-10-01 | 2009-03-12 | チャールズ スタウト, | 調節可能な融合プロモーター |
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Cited By (5)
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JP2006502714A (ja) * | 2002-10-11 | 2006-01-26 | サントリオン | 条件複製起点をもつ環状dna分子、それらの製造方法、及び、遺伝子治療におけるそれらの使用 |
JP2010057493A (ja) * | 2002-10-11 | 2010-03-18 | Centelion | 条件複製起点をもつ環状dna分子、それらの製造方法、及び、遺伝子治療におけるそれらの使用 |
KR101323542B1 (ko) * | 2002-10-11 | 2013-10-29 | 센텔리옹 에스아에스 | 조건성 복제 오리진을 보유하는 원형 dna 분자, 이의제조방법 및 이를 유전자치료에 사용하는 방법 |
JP2009509544A (ja) * | 2005-10-01 | 2009-03-12 | チャールズ スタウト, | 調節可能な融合プロモーター |
JP2016000047A (ja) * | 2005-10-01 | 2016-01-07 | スタウト, チャールズ | 調節可能な融合プロモーター |
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