JP2000514312A - ヘルパーウイルスとヘルパー依存性ベクターとから作製した改善されたアデノウイルスベクター - Google Patents
ヘルパーウイルスとヘルパー依存性ベクターとから作製した改善されたアデノウイルスベクターInfo
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- JP2000514312A JP2000514312A JP10515090A JP51509098A JP2000514312A JP 2000514312 A JP2000514312 A JP 2000514312A JP 10515090 A JP10515090 A JP 10515090A JP 51509098 A JP51509098 A JP 51509098A JP 2000514312 A JP2000514312 A JP 2000514312A
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- 229960004854 viral vaccine Drugs 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.(a)pIXコード領域の欠失または突然変異を含む約35kbより大きなサイズの ゲノムを有するヘルパーアデノウイルスと、 (b)(i)左側ITRおよび右側ITRならびにパッケージングシグナルを含 むウイルスゲノム、および (ii)そこに挿入された少なくとも1つの外来核酸配列 を有するヘルパー依存性アデノウイルスベクター とを宿主細胞へ導入することを含んでなる、パッケージングされたアデノウ イルスヘルパー依存性ベクターを作製するための方法であって、該宿主細胞 が該ヘルパー依存性アデノウイルスベクターの複製、発現およびパッケージ ングは可能にするが、該ヘルパーアデノウイルスのパッケージングは可能に しない前記方法。 2.前記ヘルパー依存性アデノウイルスベクターがウイルスゲノムの最大約35,50 0bpまでの欠失を含む、請求項1に記載の方法。 3.前記ヘルパーアデノウイルスのゲノムが、リコンビナーゼにより認識される 部位に挟まれているパッケージングシグナルを有する修飾された初期領域1 (E1)を含む、請求項1に記載の方法。 4.前記ヘルパーアデノウイルスが、Creリコンビナーゼにより認識されるloxP部 位に挟まれているパッケージングシグナルを含む、請求項2に記載の方法。 5.前記宿主細胞がCreリコンビナーゼを発現し、そしてヘルパーアデノウイルス のパッケージングシグナルを挟んでいるloxP部位の間での部位特異的な組換 えを触媒して該パッケージングシグナルの切除を誘導し、それによって、ヘ ルパーアデノウイルスのゲノムはビリオン内にパッケージングできないが、 イン・トランス(in trans)で作用して前記ヘルパー依存性アデノウイルス ベクターの複製を補完できるウイルス機能を提供することができるヘルパー アデノウイルスが得られる、請求項3に記載の方法。 6.前記ヘルパーアデノウイルスが欠失または突然変異したパッケージングシ グナルを含む、請求項1に記載の方法。 7.前記ヘルパー依存性アデノウイルスベクターが、約27kbと約35kbの間および 約13kbと約18kbの間のいずれかである、請求項1に記載の方法。 8.前記ヘルパー依存性アデノウイルスベクターが約27kbと約36kbの間であり、 かつ外来DNA挿入断片の少なくとも2つの反復コピーを含む、請求項1に記 載の方法。 9.請求項1に記載の方法により作製される、パッケージングされたヘルパー依 存性アデノウイルスベクター。 10.それ自身の核酸はビリオン内にパッケージングできないが、イン・トランス で作用して、左側ITRおよび右側ITRならびにパッケージングシグナルを含む ウイルスゲノムを有する第2のヘルパー依存性ベクターの複製を補完するヘ ルパーアデノウイルスの作製方法であって、 (a)アデノウイルスDNAを含む第1のベクター;但し、pIXをコードす るDNA配列が修飾されているかまたは欠失している、および (b)細菌の複製起点および抗生物質耐性遺伝子を含むAd5ゲノムに追加の 核酸配列が挿入されている第2のベクター をアデノウイルスベクターの複製を可能する宿主細胞に導入して、上記ヘル パーアデノウイルスを得ることを含む前記方法。 11.前記ヘルパー依存性アデノウイルスベクターがウイルスゲノムの最大約35,5 00bpまでの欠失を含む、請求項10に記載の方法。 12.前記第2のベクターが、ウイルスゲノムのE3領域に付加された核酸配列を含 む、請求項10に記載の方法。 13.前記第1のベクターがpLC8ΔpIX、pLC8ΔpIXc、pD47ElおよびpXCΔSacから なる群から選ばれる、請求項10に記載の方法。 14.前記第2のベクターがpBHG10luclおよびpBHG10stuff21からなる群から選ば れる、請求項10に記載の方法。 15.前記ヘルパーアデノウイルスがAdLC8ΔpIX、AdLC8ΔpIXlucl、AdD47Ellucl 、AdXCΔSaclucl、AdXCΔSacstuff21、およびAdD47Elstuff21からなる群か ら選ばれる、請求項10に記載の方法。 16.pIXコード領域の欠失または突然変異およびスタッファーヌクレオチド配列 が挿入されているE3領域を含む、約35kbよりも大きいサイズのゲノムを含mu ヘルパーアデノウイルス。 17.Creリコンビナーゼにより認識されるloxP部位に挟まれているパッケージン グシグナルを含む、請求項16に記載のヘルパーアデノウイルス。 18.AdLC8ΔpIX、AdLC8ΔpIXlucl、AdD47Ellucl、AdXCΔSaclucl、AdXCΔSacstu ff21およびAdD47Elstuff21からなる群から選ばれる、請求項16に記載のヘル パーアデノウイルス。 19.pIXコード領域の欠失または突然変異および修飾された初期領域1(E1)と を有する少なくとも1つのヘルパーアデノウイルスを含んでなる、E1タンパ ク質およびpIXタンパク質を発現する宿主細胞であって、該少なくとも1つ のヘルパーアデノウイルスの複製および増殖を可能にする前記宿主細胞。 20.VK10-9、VK2-20およびVK4-24からなる群から選ばれる、請求項19に記載の宿 主細胞。 21.(a)ヘルパーアデノウイルスの複製および増殖をサポートするためのE1タ ンパク質およびpIXアデノウイルスタンパク質を発現する少なくとも 1つの第1の宿主細胞;但し、この少なくとも1つの第1の宿主細胞 には該ヘルパーアデノウイルスが導入されており、該ヘルパーアデノ ウイルスは約35kbよりも大きいゲノムサイズを有し、pIXコード領 域の欠失または突然変異を含む、 (b)(i)左側ITRおよび右側ITRならびにパッケージングシグナルを含み、 かつその最大約35,500bpまでの欠失を含むウイルスゲノムと、 (ii)そこに挿入されている少なくとも1つの外来核酸配列と を有するヘルパー依存性アデノウイルスベクター、および (c)ヘルパーウイルスの存在下で該ヘルパー依存性アデノウイルスベクタ ーの複製および発現を可能にするが、該ヘルパーアデノウイルスのパ ッケージングは可能にしない、少なくとも1つの第2の宿主細胞を含 んでなる、パッケージングされたヘルパー依存性アデノウイルスベクターを 提供するためのキット。 22.前記ヘルパーアデノウイルスのゲノムが、リコンビナーゼにより認識される 部位に挟まれているパッケージングシグナルを有する修飾された初期領域1 (E1)を含む、請求項21に記載のキット。 23.前記リコンビナーゼが、前記ヘルパーアデノウイルスのloxP部位の間での部 位特異的組換えを触媒するためのCreリコンビナーゼである、請求項22に記 載のキット。 24.前記第2の宿主細胞が、前記ヘルパーアデノウイルスの部位の間での部位特 異的組換えを触媒するためのリコンビナーゼを発現し、それにより、該ヘル パーアデノウイルスのDNAをパッケージング不能にする、請求項21に記載の キット。
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US08/719,217 | 1996-09-25 | ||
US08/719,217 US6080569A (en) | 1993-06-24 | 1996-09-25 | Adenovirus vectors generated from helper viruses and helper-dependent vectors |
PCT/CA1997/000703 WO1998013510A1 (en) | 1996-09-25 | 1997-09-24 | Improved adenovirus vectors generated from helper viruses and helper-dependent vectors |
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ZA858044B (en) * | 1984-11-01 | 1987-05-27 | American Home Prod | Oral vaccines |
US4797368A (en) * | 1985-03-15 | 1989-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Adeno-associated virus as eukaryotic expression vector |
US4920211A (en) * | 1988-01-04 | 1990-04-24 | Vanderbilt University | Mutated adenovirus E1A gene for E1A promoter stimulation |
US5670488A (en) * | 1992-12-03 | 1997-09-23 | Genzyme Corporation | Adenovirus vector for gene therapy |
FR2681786A1 (fr) * | 1991-09-27 | 1993-04-02 | Centre Nat Rech Scient | Vecteurs recombinants d'origine virale, leur procede d'obtention et leur utilisation pour l'expression de polypeptides dans des cellules musculaires. |
FR2688514A1 (fr) * | 1992-03-16 | 1993-09-17 | Centre Nat Rech Scient | Adenovirus recombinants defectifs exprimant des cytokines et medicaments antitumoraux les contenant. |
WO1993019092A1 (fr) * | 1992-03-19 | 1993-09-30 | Centre National De La Recherche Scientifique | Adenovirus recombinants defectifs exprimant des proteines caracteristiques du virus epstein-barr |
AU692423B2 (en) * | 1992-09-25 | 1998-06-11 | Institut National De La Sante Et De La Recherche Medicale | Adenovirus vectors for the transfer of foreign genes into cells of the central nervous system, particularly in brain |
EP0905253A3 (en) * | 1992-12-03 | 2000-11-02 | Genzyme Corporation | Adenoviral vector deleted of all E4-ORF except ORF6 |
US6080569A (en) * | 1993-06-24 | 2000-06-27 | Merck & Co., Inc. | Adenovirus vectors generated from helper viruses and helper-dependent vectors |
US7252989B1 (en) * | 1994-04-04 | 2007-08-07 | Board Of Regents, The University Of Texas System | Adenovirus supervector system |
DE69534166T2 (de) * | 1994-10-28 | 2006-03-09 | Trustees Of The University Of Pennsylvania | Rekombinanter adenovirus und methoden zu dessen verwendung |
EP0821739B1 (en) * | 1995-04-17 | 2003-06-18 | The Board Of Regents, The University Of Texas System | An adenovirus helper-virus system |
IL122614A0 (en) * | 1995-06-15 | 1998-08-16 | Introgene Bv | Packaging systems for human recombinant adenovirus to be used in gene therapy |
-
1996
- 1996-09-25 US US08/719,217 patent/US6080569A/en not_active Expired - Lifetime
-
1997
- 1997-09-24 EP EP97941760A patent/EP0938579A1/en not_active Withdrawn
- 1997-09-24 JP JP51509098A patent/JP3803689B2/ja not_active Expired - Fee Related
- 1997-09-24 WO PCT/CA1997/000703 patent/WO1998013510A1/en not_active Application Discontinuation
- 1997-09-24 CA CA002266855A patent/CA2266855A1/en not_active Abandoned
-
1999
- 1999-11-15 US US09/440,809 patent/US6566128B1/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
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US6566128B1 (en) | 2003-05-20 |
US6080569A (en) | 2000-06-27 |
WO1998013510A1 (en) | 1998-04-02 |
JP3803689B2 (ja) | 2006-08-02 |
EP0938579A1 (en) | 1999-09-01 |
CA2266855A1 (en) | 1998-04-02 |
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