JPH09507753A - 普遍的なドナー細胞及びキメラ性哺乳類宿主のための相同組換え - Google Patents
普遍的なドナー細胞及びキメラ性哺乳類宿主のための相同組換えInfo
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- JPH09507753A JPH09507753A JP7518161A JP51816195A JPH09507753A JP H09507753 A JPH09507753 A JP H09507753A JP 7518161 A JP7518161 A JP 7518161A JP 51816195 A JP51816195 A JP 51816195A JP H09507753 A JPH09507753 A JP H09507753A
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.機能的な主要組織適合複合体(MHC)抗原の発現に関連する遺伝子の個々の 遺伝子座での損傷の導入の結果として前記MHC 抗原を欠く遺伝学的に構築された 哺乳類細胞であって、ここで前記遺伝子が IFNγR遺伝子であり、前記導入が前 記遺伝子座の少なくとも一部と相同の配列及び前記損傷を含んで成る少なくとも 1つのDNA 標的化構造体による前記哺乳類細胞のトランスフェクション及び前記 遺伝子座での前記構造体の組込みにより達成されることを特徴とする哺乳類細胞 。 2.機能的な主要組織適合複合体(MHC)抗原の発現に関連する遺伝子の個々の 遺伝子座での損傷の導入の結果として前記MHC 抗原を欠く遺伝学的に構築された 哺乳類細胞であって、ここで前記DNA 構造体が、5′から3′の方向に、標的遺 伝子座に相同の領域、検出のためのリガンドに結合するエピトープに連結される MHC 抗原の発現に関連する遺伝子の上流の外来性プロモーター/エンハンサー、 及び選択可能マーカー遺伝子、並びに標的遺伝子座に相同の第2領域をコードす るDNA を含んで成り、それにより、前記細胞が前記DNA 標的化構造体によりトラ ンスフェクトされ、そして相同的に組換えられる場合、融合タンパク質が発現さ れ、そして検出のために前記細胞外に分泌されることを特徴とする哺乳類細胞。 3.MHC 抗原の発現に関連する前記遺伝子が IFNγR遺伝子であり、そして前 記標的化構造体が IFNγRタンパク質のトランスメンブランコード領域に連結さ れる転写的に且つ翻訳的に弱められた陽性の選択可能マーカー遺伝子をコードす るDNA を含んで成り、前記DNA は、前記選択可能マーカーが前記膜の細胞質側上 で機能的であり、そして発現されるように、細胞膜内で融合タンパク質として発 現される請求の範囲第2項記載の哺乳類細胞。 4.5′から3′の方向に、標的遺伝子座に相同の領域、検出のためのリガン ドに結合するエピトープに連結されるMHC 抗原の発現に関連する遺伝子の上流の 外来性プロモーター/エンハンサー、及び選択可能マーカー遺伝子、並びに標的 遺伝子座に相同の第2領域をコードするDNA を含んで成るDNA 構造体であって、 前記DNA 構造体が哺乳類宿主において発現することができることを特徴とするDN A 構造体。 5.内在膜タンパク質のトランスメンブランコード領域に連結される、転写的 に且つ翻訳的に弱められた陽性の選択可能マーカー遺伝子をコードするDNA を含 んで成るDNA 構造体。 6.前記内在膜タンパク質が IFNγRであり、そして前記選択可能マーカー遺 伝子が耐ネオマイシン性遺伝子である請求の範囲第5項記載のDNA 構造体。 7.IFNγR遺伝子の不活性化の結果として機能的MHC 抗原を欠く遺伝学的に 構築された哺乳類細胞を、少なくとも1つのDNA 構造体による前記哺乳類細胞の トランスフェクションにより生成するための方法であって、ここで前記DNA 構造 体が、それ自体のDNA 構造体及び宿主細胞の染色体に存在する前記遺伝子の少な くとも一部と相同の少なくとも 100bpのDNA 配列を含んで成る前記宿主細胞の選 択のための選択可能マーカー遺伝子を含んで成り; 前記DNA 構造体により宿主哺乳類細胞をトランスフェクトし、ここで前記構造 体が相同組換えにより前記染色体中に組込まれ、それによって前記遺伝子を不活 性化し、トランスフェクトされた細胞を生成し; 前記不活性化された遺伝子を担持する細胞を検出することによって機能的MHC 抗原を欠くトランスフェクトされた細胞を選択するこ とを含んで成る方法。 8.機能的MHC 抗原の発現に関連する遺伝子の不活性化の結果としてそのMHC 抗原を欠く遺伝学的に構築された哺乳類細胞を、少なくとも1つのDNA 構造体に よる前記哺乳類細胞のトランスフェクションにより生成するための方法であって 、ここで前記構造体がそれ自体のDNA 構造体及び宿主細胞の染色体に存在する前 記遺伝子の少なくとも一部と相同の少なくとも 100bpのDNA 配列を含んで成る前 記宿主細胞の選択のための選択可能マーカー遺伝子を含んで成り; 前記DNA 構造体により宿主哺乳類細胞をトランスフェクトし、ここで前記DNA 構造体が、5′から3′の方向に、標的遺伝子座に相同の領域、検出のためにリ ガンドに結合するエピトープに連結される前記 IFNγR遺伝子の上流の外来性プ ロモーター/エンハンサー及び選択可能マーカー遺伝子、並びに標的遺伝子座に 相同の第2領域をコードするDNA を含んで成り、それにより、前記細胞がトラン スフェクトされ、そして前記DNA 標的化構造体により相同的に組換えられる場合 、融合タンパク質が前記細胞の内部で発現され又は検出のために前記細胞外に分 泌され;そして 機能的MHC 抗原を欠いているトランスフェクトされた細胞を選択することを含 んで成る方法。 9.前記MHC 抗原の発現に関連する前記遺伝子が IFNγR遺伝子であり、そし て前記標的化構造体が IFNγRタンパク質のトランスメンブランコード領域に連 結される転写的に且つ翻訳的に弱められた陽性の選択可能マーカー遺伝子をコー ドするDNA を含んで成り、前記DNA は、前記選択可能マーカーが前記膜の細胞質 側上で機能的であり、そして発現されるように、細胞膜内で融合タンパク質とし て発現される請求の範囲第8項記載の方法。 10.哺乳類細胞における染色体の標的遺伝子を不活性化するため に相同組換えの検出を高めるための方法であって: a)5′から3′の方向に、標的遺伝子座に相同の領域、検出のためのリガン ドに結合するエピトープに連結されるMHC 抗原の発現に関連する遺伝子の上流の 外来性プロモーター/エンハンサー、及び選択可能マーカー遺伝子、並びに標的 遺伝子に相同の第2領域をコードするDNA を含んで成る少なくとも1つのDNA 構 造体により前記哺乳類細胞をトランスフェクトし、その結果、前記構造体が相同 組換えにより前記染色体中に組込まれ、それにより前記標的遺伝子を不活性化し 、そして発現され、そして細胞外に分泌される融合タンパク質を生成し; b)前記選択可能マーカー遺伝子を用いて選択し;そして c)前記融合タンパク質を生成する宿主細胞をスクリーンすることを含んで成 る方法。 11.哺乳類細胞における内在性膜タンパク質をコードする遺伝子を不活性化す るために相同組換えの検出を高めるための方法であって: a)内在性膜タンパク質のトランスメンブランコード領域に連結される、転写 的に及び翻訳的に弱められた陽性の選択可能マーカー遺伝子をコードするDNA を 含んで成る少なくとも1つのDNA 構造体により前記哺乳類細胞をトランスフェク トし、その結果、前記構造体が相同組換えにより前記哺乳類細胞における染色体 中に組込まれ、それにより、前記標的遺伝子を不活性化し、そして前記選択可能 マーカーが前記膜の細胞質側で機能し、そして発現されるように細胞膜内で発現 される融合タンパク質を生成し;そして b)前記融合遺伝子生成物を生成する宿主細胞を選択することを含んで成る方 法。 12.哺乳類宿主における移植片拒絶を防止するために治療剤の有 効性を決定するための方法であって: a)前記治療剤を前記哺乳類宿主に投与し、ここで前記宿主は、機能的MHC 抗 原を欠き、そして移植される、遺伝的に構築された組織又は細胞を有することに より特徴づけられており;そして b)前記治療剤に応じて時間にわたって前記移植された組織又は細胞の拒絶の 存在又は不在を決定することを含んで成る方法。
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US08/175,469 | 1993-12-30 | ||
US08/175,469 US5574205A (en) | 1989-07-25 | 1993-12-30 | Homologous recombination for universal donor cells and chimeric mammalian hosts |
PCT/US1994/014888 WO1995017911A1 (en) | 1993-12-30 | 1994-12-28 | Homologous recombination for universal donor cells and chimeric mammalian hosts |
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AT (1) | ATE363919T1 (ja) |
AU (1) | AU696372B2 (ja) |
CA (1) | CA2180019A1 (ja) |
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US5413923A (en) * | 1989-07-25 | 1995-05-09 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
EP0950707B1 (en) | 1989-07-25 | 2009-02-18 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
CA2112673A1 (en) * | 1991-07-01 | 1993-01-21 | Raju Kucherlapati | Interstitial deletion in chromosomal dna |
WO1994021787A1 (en) * | 1993-03-15 | 1994-09-29 | Cell Genesys, Inc. | Method for defined deletions of dna |
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1993
- 1993-12-30 US US08/175,469 patent/US5574205A/en not_active Expired - Lifetime
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1994
- 1994-12-28 EP EP95906116A patent/EP0742723B1/en not_active Expired - Lifetime
- 1994-12-28 AU AU14456/95A patent/AU696372B2/en not_active Ceased
- 1994-12-28 WO PCT/US1994/014888 patent/WO1995017911A1/en active IP Right Grant
- 1994-12-28 AT AT95906116T patent/ATE363919T1/de not_active IP Right Cessation
- 1994-12-28 DE DE69434986T patent/DE69434986T2/de not_active Expired - Fee Related
- 1994-12-28 CA CA002180019A patent/CA2180019A1/en not_active Abandoned
- 1994-12-28 JP JP51816195A patent/JP3734831B2/ja not_active Expired - Fee Related
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1995
- 1995-05-18 US US08/443,613 patent/US6514752B1/en not_active Expired - Fee Related
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JP2020202880A (ja) * | 2011-04-20 | 2020-12-24 | ザ ユニバーシティ オブ ワシントン スルー イッツ センター フォー コマーシャライゼーションThe University Of Washington Through Its Center For Commercialization | β2ミクログロブリン欠損細胞 |
JP2017060519A (ja) * | 2011-12-22 | 2017-03-30 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 発現ベクター構成、新規の産生細胞生成法、およびポリペプチドの組換え産生のためのそれらの使用 |
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JP2021072867A (ja) * | 2011-12-22 | 2021-05-13 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 発現ベクター構成、新規の産生細胞生成法、およびポリペプチドの組換え産生のためのそれらの使用 |
JP2017508468A (ja) * | 2014-03-11 | 2017-03-30 | セレクティスCellectis | 同種移植に適合するt細胞を作製するための方法 |
JP2020114229A (ja) * | 2014-03-11 | 2020-07-30 | セレクティスCellectis | 同種移植に適合するt細胞を作製するための方法 |
JP2022513490A (ja) * | 2018-12-16 | 2022-02-08 | フィジーン、エルエルシー | 遺伝子編集線維芽細胞の治療的使用 |
Also Published As
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---|---|
US5574205A (en) | 1996-11-12 |
DE69434986T2 (de) | 2008-02-07 |
JP3734831B2 (ja) | 2006-01-11 |
WO1995017911A1 (en) | 1995-07-06 |
AU1445695A (en) | 1995-07-17 |
DE69434986D1 (de) | 2007-07-19 |
EP0742723A1 (en) | 1996-11-20 |
US6139835A (en) | 2000-10-31 |
CA2180019A1 (en) | 1995-07-06 |
AU696372B2 (en) | 1998-09-10 |
ATE363919T1 (de) | 2007-06-15 |
EP0742723A4 (en) | 2002-05-08 |
US6514752B1 (en) | 2003-02-04 |
EP0742723B1 (en) | 2007-06-06 |
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