JPH11509084A - 選択された物質の細胞内への輸送に用いるためのキメラ蛋白質 - Google Patents
選択された物質の細胞内への輸送に用いるためのキメラ蛋白質Info
- Publication number
- JPH11509084A JPH11509084A JP9501009A JP50100997A JPH11509084A JP H11509084 A JPH11509084 A JP H11509084A JP 9501009 A JP9501009 A JP 9501009A JP 50100997 A JP50100997 A JP 50100997A JP H11509084 A JPH11509084 A JP H11509084A
- Authority
- JP
- Japan
- Prior art keywords
- human
- receptor
- chimeric protein
- cells
- domain
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.選択物質に結合するアミノ酸配列を有する機能的ドメインと、哺乳類にお いて選択物質に通常結合する哺乳類細胞表面受容体以外の哺乳類細胞表面受容体 に結合するアミノ酸配列を有する担体ドメインとを含む、キメラ蛋白質。 2.哺乳類細胞表面受容体がヒト細胞表面受容体である、請求項1記載のキメ ラ蛋白質。 3.ヒト細胞表面受容体が、ヒト低密度リポ蛋白質受容体、ヒトトランスフェ リン受容体、ヒト血清アルブミン受容体、ヒトアシアロ糖蛋白質受容体、ヒトア デノウイルス受容体、ヒトレトロウイルス受容体、ヒトCD4、ヒトリポ蛋白質(a) 受容体、ヒト免疫グロブリンFc受容体、ヒトa-フェトプロテイン受容体、ヒトLD LR様蛋白質(LRP)受容体、ヒトアセチル化LDL受容体、ヒトマンノース受容体、 およびヒトマンノース-6-リン酸受容体からなる群より選択される、請求項2記載 のキメラ蛋白質。 4.選択物質がLDLコレステロールであり、機能的ドメインがヒト低密度リポ 蛋白質受容体のリガンド結合ドメインのアミノ酸配列を含む、請求項2記載のキ メラ蛋白質。 5.担体ドメインが 低密度リポ蛋白質受容体以外のヒト細胞表面受容体と結 合するアミノ酸配列を含む、請求項4記載のキメラ蛋白質。 6.ヒト細胞表面受容体がヒトトランスフェリン受容体である、請求項5記載 のキメラ蛋白質。 7.選択物質に結合するアミノ酸配列を有する機能的ドメインと、哺乳類にお いて選択物質に通常結合する哺乳類細胞表面受容体以外の哺乳類細胞表面受容体 に結合するアミノ酸配列を有する担体ドメインとを含むキメラ蛋白質をコードす るDNA。 8.哺乳類細胞表面受容体がヒト細胞表面受容体である、キメラ蛋白質をコー ドする請求項7記載のDNA。 9.ヒト細胞表面受容体が、ヒト低密度リポ蛋白質受容体、ヒトトランスフェ リン受容体、ヒト血清アルブミン受容体、ヒトアシアロ糖蛋白質受容体、ヒトア デノウイルス受容体、ヒトレトロウイルス受容体、ヒトCD4、ヒトリポ蛋白質(a) 受 容体、ヒト免疫グロブリンFc受容体、ヒトa-フェトプロテイン受容体、ヒトLDLR 様蛋白質(LRP)受容体、ヒトアセチル化LDL受容体、ヒトマンノース受容体、お よびヒトマンノース-6-リン酸受容体からなる群より選択される、請求項8記載の DNA。 10.ヒト低密度リポ蛋白質受容体のリガンド結合ドメインのアミノ酸配列を有 する機能的ドメインと、ヒトトランスフェリン受容体に結合するアミノ酸配列を 有する担体ドメインとを含むキメラ蛋白質をコードするDNA。 11.a)プロモーター、 b)選択物質に結合するアミノ酸配列を有する機能的ドメインと、哺乳類において 選択物質に通常結合する哺乳類細胞表面受容体以外の哺乳類細胞表面受容体に結 合するアミノ酸配列を有する担体ドメインとを含むキメラ蛋白質をコードするDN A を含み、該キメラ蛋白質をコードするDNAの発現が該プロモーターの制御下にあ る、発現プラスミド。 12.選択物質に結合するアミノ酸配列を有する機能的ドメインと、哺乳類にお いて選択物質に通常結合する哺乳類細胞表面受容体以外の哺乳類細胞表面受容体 に結合するアミノ酸配列を有する担体ドメインとを含むキメラ蛋白質をコードす るDNAを発現する、遺伝的に改変された哺乳類細胞。 13.哺乳類細胞表面受容体がヒト細胞表面受容体である、請求項12記載の遺伝 的に改変された哺乳類細胞。 14.選択物質がLDLコレステロールであり、ヒト細胞表面受容体がヒトトラン スフェリン受容体である、請求項13記載の遺伝的に改変された哺乳類細胞。 15.機能的ドメインがヒト低密度リポ蛋白質受容体のリガンド結合ドメインの アミノ酸配列を含む、請求項14記載の遺伝的に改変された哺乳類細胞。 16.ヒト細胞表面受容体が、ヒト低密度リポ蛋白質受容体、ヒトトランスフェ リン受容体、ヒト血清アルブミン受容体、ヒトアシアロ糖蛋白質受容体、ヒトア デノウイルス受容体、ヒトレトロウイルス受容体、ヒトCD4、ヒトリポ蛋白質(a) 受容体、ヒト免疫グロブリンFc受容体、ヒトa-フェトプロテイン受容体、ヒトLD LR様蛋白質(LRP)受容体、ヒトアセチル化LDL受容体、ヒトマンノース受容体、 およびヒトマンノース-6-リン酸受容体からなる群より選択される、請求項13記 載の遺伝的に改変された哺乳類細胞。 17.哺乳類細胞が、ヒト細胞、ブタ細胞、ハムスター細胞、ウシ属の細胞、イ ヌ科の細胞、マウス細胞、ラット細胞、サル細胞、ネコ科の細胞、ウサギ細胞、 ヒツジ細胞、およびチンパンジー細胞からなる群より選択される、請求項12記載 の遺伝的に改変された哺乳類細胞。 18.ヒト細胞が、ヒト線維芽細胞、ヒト表皮角化細胞、ヒト上皮細胞、ヒト卵 巣細胞、ヒト内皮細胞、ヒトグリア細胞、ヒト神経細胞、血液の有形要素、ヒト 筋細胞、ヒト肝細胞、およびこれらのヒト細胞種の前駆体からなる群より選択さ れる、請求項17記載の遺伝的に改変されたヒト細胞。 19.哺乳類細胞がチャイニーズハムスターの卵巣細胞である、請求項17記載の 遺伝的に改変された哺乳類細胞。 20.細胞が不死化細胞である、請求項17記載の遺伝的に改変された哺乳類細胞 。 21.細胞が一次細胞または二次細胞である、請求項18記載の遺伝的に改変され たヒト細胞。 22.DNAがキメラ蛋白質をコードし、その機能的ドメインがヒト低密度リポ蛋 白質受容体のリガンド結合ドメインのアミノ酸配列を含み、その担体ドメインが 、ヒトトランスフェリン受容体と結合するヒトトランスフェリンのアミノ酸配列 を含む、請求項12記載の遺伝的に改変された哺乳類細胞。 23.DNAがキメラ蛋白質をコードし、その機能的ドメインがヒト低密度リポ蛋 白質受容体のリガンド結合ドメインのアミノ酸配列を含み、その担体ドメインが 、ヒトトランスフェリン受容体と結合するヒトトランスフェリンのアミノ酸配列 を含む、請求項17記載の遺伝的に改変された哺乳類細胞。 24.DNAがキメラ蛋白質をコードし、その機能的ドメインがヒト低密度リポ蛋 白質受容体のリガンド結合ドメインのアミノ酸配列を含み、その担体ドメインが 、ヒトトランスフェリン受容体と結合するヒトトランスフェリンのアミノ酸配列 を含む、請求項18記載の遺伝的に改変された哺乳類細胞。 25.DNAがキメラ蛋白質をコードし、その機能的ドメインがヒト低密度リポ蛋 白 質受容体のリガンド結合ドメインのアミノ酸配列を含み、その担体ドメインが、 ヒトトランスフェリン受容体と結合するヒトトランスフェリンのアミノ酸配列を 含む、請求項19記載の遺伝的に改変された哺乳類細胞。 26.DNAがキメラ蛋白質をコードし、その機能的ドメインがヒト低密度リポ蛋 白質受容体のリガンド結合ドメインのアミノ酸配列を含み、その担体ドメインが 、ヒトトランスフェリン受容体と結合するヒトトランスフェリンのアミノ酸配列 を含む、請求項20記載の遺伝的に改変された哺乳類細胞。 27.DNAがキメラ蛋白質をコードし、その機能的ドメインがヒト低密度リポ蛋 白質受容体のリガンド結合ドメインのアミノ酸配列を含み、その担体ドメインが 、ヒトトランスフェリン受容体と結合するヒトトランスフェリンのアミノ酸配列 を含む、請求項21記載の遺伝的に改変された哺乳類細胞。 28.低密度リポ蛋白質と低密度リポ蛋白質のリガンド結合ドメインとの結合、 およびそのキメラ蛋白質の担体ドメインのアミノ酸配列とそのヒト細胞上の細胞 表面受容体との結合に適した条件であって、その結合によってキメラ蛋白質と低 密度リポ蛋白質との複合体が形成され、該複合体がエンドサイトーシスによって 細胞内に輸送される条件下において、 低密度リポ蛋白質を、 a)ヒト低密度リポ蛋白質受容体のリガンド結合ドメインのアミノ酸配列を有する 機能的ドメインと、ヒト低密度リポ蛋白質受容体以外のヒト細胞表面受容体に結 合するアミノ酸配列を有する担体ドメインとを含むキメラ蛋白質、および b)該キメラ蛋白質の担体ドメインのアミノ酸配列に結合する表面受容体を保持す るヒト細胞 と結合させることを含む、低密度リポ蛋白質を細胞内へ輸送する方法。 29.担体ドメインが、ヒト低密度リポ蛋白質受容体、ヒトトランスフェリン受 容体、ヒト血清アルブミン受容体、ヒトアシアロ糖蛋白質受容体、ヒトアデノウ イルス受容体、ヒトレトロウイルス受容体、ヒトCD4、ヒトリポ蛋白質(a)受容体 、ヒト免疫グロブリンFc受容体、ヒトa-フェトプロテイン受容体、ヒトLDLR様蛋 白質(LRP)受容体、ヒトアセチル化LDL受容体、ヒトマンノース受容体、および ヒトマンノース-6-リン酸受容体からなる群より選択されるヒト細胞表面受容体 と 結合する、請求項28記載の方法。 30.担体ドメインが、ヒト細胞上の細胞表面受容体と結合するヒトトランスフ ェリンのアミノ酸配列を含む、請求項28記載の方法。 31.ヒト低密度リポ蛋白質受容体のリガンド結合ドメインのアミノ酸配列を有 する機能的ドメインと、ヒト低密度リポ蛋白質受容体以外のヒト細胞表面受容体 に結合するアミノ酸配列を有する担体ドメインとを含むキメラ蛋白質を、個体に 投与することを含む、個体の血流内の低密度リポ蛋白質のレベルを低下させる方 法であって、該個体の血流内の低密度リポ蛋白質が該キメラ蛋白質中の低密度リ ポ蛋白質のリガンド結合ドメインに結合し、該キメラ蛋白質の担体ドメインがヒ ト細胞表面受容体に結合し、それによって低密度リポ蛋白質を結合させたキメラ 蛋白質が該細胞表面受容体を保持する細胞内に輸送され、それによって該個体の 血流内の低密度リポ蛋白質のレベルを低下させる方法。 32.担体ドメインが、ヒト低密度リポ蛋白質受容体、ヒトトランスフェリン受 容体、ヒト血清アルブミン受容体、ヒトアシアロ糖蛋白質受容体、ヒトアデノウ イルス受容体、ヒトレトロウイルス受容体、ヒトCD4、ヒトリポ蛋白質(a)受容体 、ヒト免疫グロブリンFc受容体、ヒトa-フェトプロテイン受容体、ヒトLDLR様蛋 白質(LRP)受容体、ヒトアセチル化LDL受容体、ヒトマンノース受容体、および ヒトマンノース-6-リン酸受容体からなる群より選択されるヒト細胞表面受容体 と結合する、請求項31記載の方法。 33.担体ドメインが、ヒトトランスフェリン受容体と結合するヒトトランスフ ェリンのアミノ酸配列を含む、請求項31記載の方法。 34.請求項1、2、3、4、5、または6に記載のキメラ蛋白質を含む薬学的組成物 。 35.請求項12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、 または27に記載の遺伝的に改変された細胞を含む薬学的組成物。 36.細胞表面受容体、キメラ蛋白質、および選択物質が複合体を形成し、該複 合体が細胞表面受容体に結合して、受容体を介したエンドサイトーシスによって 細胞内に輸送されるように、機能的ドメインで選択物質に結合し担体ドメインで 哺乳類細胞上の細胞表面受容体に結合するキメラ蛋白質に、哺乳類細胞を接触さ せることを含む、選択物質を哺乳類細胞内に導入する方法。 37.選択物質が、アセチル化低密度リポ蛋白質、アポリポ蛋白質E4、腫瘍壊死 因子a、トランスフォーミング増殖因子β、サイトカイン、免疫グロブリン、ホ ルモン、グルコース、胆汁酸塩、糖脂質、またはグリコサミノグリカンからなる 群より選択される、請求項36記載の方法。 38.細胞表面受容体およびキメラ蛋白質が複合体を形成し、該複合体が細胞表 面受容体に結合して、受容体を介したエンドサイトーシスによって細胞内に輸送 されるように、機能的ドメインを有し、担体ドメインで哺乳類細胞上の細胞表面 受容体に結合するキメラ蛋白質に、哺乳類細胞を接触させることを含む、哺乳類 細胞に機能的蛋白質ドメインを導入する方法。 39.機能的蛋白質ドメインが、酵素活性を有するアミノ酸配列を含む、請求項 38記載の方法。 40.機能的蛋白質ドメインが、DNAまたはRNA配列に結合するアミノ酸配列を含 み、その哺乳類細胞における遺伝子発現を増強または低下させる、請求項38記載 の方法。 41.機能的蛋白質ドメインが、哺乳類細胞における選択された蛋白質、炭水化 物、脂質、または糖脂質の標的と結合する、請求項38記載の方法。 42.哺乳類細胞をそのキメラ蛋白質とインビボで接触させる、請求項36、37、 38、39、40、または41に記載の方法。 43.治療、予防、または診断に用いるための、請求項1〜6のいずれか一項に記 載のキメラ蛋白質、請求項7〜10のいずれか一項に記載のDNA、請求項11記載の発 現プラスミド、または請求項12〜27のいずれか一項に記載の細胞。 44.循環している物質または病原体、例えば細胞外液(例えば、血液またはリ ンパ液)中を循環している物質または病原体などのレベルを低下させるための、 請求項43記載の蛋白質、DNA、プラスミド、または細胞。 45.選択物質を、細胞(例えば哺乳類細胞)に導入する(例えば、輸送する) ための、請求項43記載の蛋白質、DNA、プラスミド、または細胞。 46.選択物質または病原体の、細胞(例えば哺乳類細胞)への取り込みを増加 させるための、請求項43記載の蛋白質、DNA、プラスミド、または細胞。 47.選択物質または病原体を隔離するための、請求項43記載の蛋白質、DNA、 プラスミド、または細胞。 48.治療または予防に用いるための、ヒト低密度リポ蛋白質受容体のリガンド 結合ドメインのアミノ酸配列を有する機能的ドメインと、ヒト低密度リポ蛋白質 受容体以外のヒト細胞表面受容体に結合するアミノ酸配列を有する担体ドメイン とを含むキメラ蛋白質であって、その治療または予防に、例えば、低密度リポ蛋 白質と低密度リポ蛋白質のリガンド結合ドメインとの結合、および該キメラ蛋白 質の担体ドメインのアミノ酸配列とそのヒト細胞上の細胞表面受容体との結合に 適した条件であって、その結合によりキメラ蛋白質と低密度リポ蛋白質との複合 体が形成され、該複合体がエンドサイトーシスによって細胞内に輸送される条件 下において、低密度リポ蛋白質をキメラ蛋白質と結合させることによって、低密 度リポ蛋白質をヒト細胞に輸送することが含まれる、キメラ蛋白質。 49.担体ドメインが、ヒト低密度リポ蛋白質受容体、ヒトトランスフェリン受 容体、ヒト血清アルブミン受容体、ヒトアシアロ糖蛋白質受容体、ヒトアデノウ イルス受容体、ヒトレトロウイルス受容体、ヒトCD4、ヒトリポ蛋白質(a)受容体 、ヒト免疫グロブリンFc受容体、ヒトα-フェトプロテイン受容体、ヒトLDLR様 蛋白質(LRP)受容体、ヒトアセチル化LDL受容体、ヒトマンノース受容体、およ びヒトマンノース-6-リン酸受容体からなる群より選択されるヒト細胞表面受容 体と結合する、請求項48記載のキメラ蛋白質。 50.担体ドメインが、ヒト細胞上の細胞表面受容体と結合するヒトトランスフ ェリンのアミノ酸配列を含む、請求項48または49記載のキメラ蛋白質。 51.治療または予防に用いるための、ヒト低密度リポ蛋白質受容体のリガンド 結合ドメインのアミノ酸配列を有する機能的ドメインと、ヒト低密度リポ蛋白質 受容体以外のヒト細胞表面受容体に結合するアミノ酸配列を有する担体ドメイン とを含むキメラ蛋白質であって、その治療または予防に、例えば、キメラ蛋白質 を個体に投与し、それによって該個体の血流内の低密度リポ蛋白質が該キメラ蛋 白質中の低密度リポ蛋白質のリガンド結合ドメインと結合し、該キメラ蛋白質の 担体ドメインがヒト細胞表面受容体と結合し、その結合により低密度リポ蛋白質 を結合させたキメラ蛋白質が該細胞表面受容体を保持する細胞内に輸送され、そ れによって該個体の血流内の低密度リポ蛋白質のレベルを低下させることによっ て、個体の血流内の低密度リポ蛋白質のレベルを低下させることが含まれる、キ メラ蛋白質。 52.担体ドメインが、ヒト低密度リポ蛋白質受容体、ヒトトランスフェリン受 容体、ヒト血清アルブミン受容体、ヒトアシアロ糖蛋白質受容体、ヒトアデノウ イルス受容体、ヒトレトロウイルス受容体、ヒトCD4、ヒトリポ蛋白質(a)受容体 、ヒト免疫グロブリンFc受容体、ヒトα-フェトプロテイン受容体、ヒトLDLR様 蛋白質(LRP)受容体、ヒトアセチル化LDL受容体、ヒトマンノース受容体、およ びヒトマンノース-6-リン酸受容体からなる群より選択されるヒト細胞表面受容 体と結合する、請求項51記載のキメラ蛋白質。 53.担体ドメインが、ヒトトランスフェリン受容体と結合するヒトトランスフ ェリンのアミノ酸配列を含む、請求項51記載のキメラ蛋白質。 54.治療または予防に用いるための、機能的ドメインで選択物質に結合し担体 ドメインで哺乳類細胞上の細胞表面受容体に結合するキメラ蛋白質であって、そ の治療または予防に、例えば、細胞表面受容体、キメラ蛋白質、および選択物質 が複合体を形成し、該複合体が細胞表面受容体と結合して、受容体を介したエン ドサイトーシスによって細胞内に輸送されるように、哺乳類細胞を該キメラ蛋白 質に接触させることによって、哺乳類細胞に選択物質を導入することが含まれる 、キメラ蛋白質。 55.選択物質が、アセチル化低密度リポ蛋白質、アポリポ蛋白質E4、腫瘍壊死 因子a、トランスフォーミング増殖因子β、サイトカイン、免疫グロブリン、ホ ルモン、グルコース、胆汁酸塩、糖脂質、またはグリコサミノグリカンからなる 群より選択される、請求項54記載のキメラ蛋白質。 56.治療または予防に用いるための、機能的ドメインを有し、担体ドメインで 哺乳類細胞上の細胞表面受容体に結合するキメラ蛋白質であって、その治療また は予防に、例えば、細胞表面受容体、キメラ蛋白質、および選択物質が複合体を 形成し、該複合体が細胞表面受容体に結合して、受容体を介したエンドサイトー シスによって細胞内に輸送されるように、該細胞を該キメラ蛋白質に接触させる ことによって、哺乳類細胞に機能的蛋白質ドメインを導入することが含まれる、 キメラ蛋白質。 57.機能的蛋白質ドメインが、酵素活性を有するアミノ酸配列を含む、請求項 56記載のキメラ蛋白質。 58.機能的蛋白質ドメインが、DNAまたはRNA配列と結合するアミノ酸配列を含 み、その哺乳類細胞における遺伝子発現を増強または低下させる、請求項56記載 のキメラ蛋白質。 59.機能的蛋白質ドメインが、その哺乳類細胞における選択された蛋白質、炭 水化物、脂質、または糖脂質の標的と結合する、請求項56記載のキメラ蛋白質。 60.接触の段階がインビボで実施される、請求項48〜50、および54〜59のいず れか一項に記載のキメラ蛋白質。 61.治療、予防、または診断に用いるための、請求項1〜6のいずれか一項に記 載のキメラ蛋白質、請求項7〜10のいずれか一項に記載のDNA、請求項11記載の発 現プラスミド、または請求項12〜27のいずれか一項に記載の細胞を含む、薬学的 組成物、移植片(graft)または埋没物(implant)。
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Cited By (3)
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WO2009041037A1 (ja) * | 2007-09-26 | 2009-04-02 | Japan As Represented By The President Of National Cardiovascular Center | 体内に存在する病因物質の低下剤 |
JP5429804B2 (ja) * | 2007-09-26 | 2014-02-26 | 独立行政法人国立循環器病研究センター | 体内に存在する病因物質の低下剤 |
US8834887B2 (en) | 2007-09-26 | 2014-09-16 | National Cerebral And Cardiovascular Center | Drug for suppressing pathogen occurring in vivo |
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MY137300A (en) | 2009-01-30 |
CN1190438A (zh) | 1998-08-12 |
EP0832225A1 (en) | 1998-04-01 |
HK1015414A1 (en) | 1999-10-15 |
DE69636621D1 (de) | 2006-11-23 |
AU6148296A (en) | 1996-12-24 |
US6262026B1 (en) | 2001-07-17 |
JP4276295B2 (ja) | 2009-06-10 |
CA2221711A1 (en) | 1996-12-12 |
ATE342357T1 (de) | 2006-11-15 |
NZ310657A (en) | 2000-01-28 |
WO1996039510A1 (en) | 1996-12-12 |
KR100509261B1 (ko) | 2008-11-07 |
CN1161465C (zh) | 2004-08-11 |
TW517060B (en) | 2003-01-11 |
DE69636621T2 (de) | 2007-08-30 |
US6858578B2 (en) | 2005-02-22 |
US6027921A (en) | 2000-02-22 |
AU723350B2 (en) | 2000-08-24 |
US20010025026A1 (en) | 2001-09-27 |
IL122381A (en) | 2008-07-08 |
US5817789A (en) | 1998-10-06 |
IL122381A0 (en) | 1998-06-15 |
KR19990022535A (ko) | 1999-03-25 |
EP0832225B1 (en) | 2006-10-11 |
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