JP7134944B2 - 遺伝子改変免疫不全非ヒト動物における改良されたヒト赤血球生存に関連する方法および組成物 - Google Patents
遺伝子改変免疫不全非ヒト動物における改良されたヒト赤血球生存に関連する方法および組成物 Download PDFInfo
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Description
本発明は、アメリカ国立衛生研究所によって授与された補助金番号第R24 ODO18259のもとの政府支援により行われた。政府は、本発明において一定の権利を有する。
本願は、2016年8月11日に出願された米国仮特許出願第62/373,671号の優先権を主張し、その内容全体が参照によって本明細書に組み込まれる。
MD1:NOD.Cg-PrkdcscidIl2rgtm1Wjl/Lyst<em1Mvw>/Sz(マウスLyst遺伝子からの配列番号1の欠失によりLystがノックアウトされたNSGマウス系統)
MD2:NSG CD47 KO Tg(hCD47)(マウスCD47がノックアウトされヒトCD47をコードする導入遺伝子を含むNSGマウス系統)
MD3:NSG CSF1r-HTK(CSF1rプロモーターがヘルペスチミジンキナーゼの発現を駆動する導入遺伝子を含むNSGマウス系統)
MD4:B6.129S-Rag1<tm1Mom>CD47 KO Il2rg<tm1Wjl>/Sz(マウスIL2rgがノックアウトされマウスCD47がノックアウトされたBL/6マウス系統で、BL/6 Rag1nullCD47 KO IL2rgnullとも呼ばれる)
プライマー番号1578
GGGTGAATATTGAAGTTCTGAGAC(配列番号3)
プライマー番号1579
CATTTGAATCCTGTCTCAGAATGA(配列番号4)
プライマー番号1580
GCCACCAAAGAACAGGTCCTTT(配列番号5)
プライマー番号1581
GAAGTGGGAATACTCACAACGC(配列番号6)
95℃-30秒間
95℃-15秒間}
60℃-30秒間}30×サイクル
68℃-1分間}
68℃-5分間
4℃-保持
Claims (15)
- Lystnull免疫不全マウスである、マクロファージおよび/またはマクロファージ抗ヒト赤血球活性を欠損している、遺伝子改変免疫不全マウス。
- ベージュ変異Lystbgについてホモ接合であるNOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJマウスである、マクロファージおよび/またはマクロファージ抗ヒト赤血球活性を欠損している、遺伝子改変免疫不全マウス。
- ベージュ変異Lystbgについてホモ接合であるNOD.Cg-Rag1tm1MomIl2rgtm1Wjl/SzJマウスである、マクロファージおよび/またはマクロファージ抗ヒト赤血球活性を欠損している、遺伝子改変免疫不全マウス。
- NOD.Cg-PrkdcscidIl2rgtm1Wjl/Lystem1Mvw/Szマウスである、マクロファージおよび/またはマクロファージ抗ヒト赤血球活性を欠損している、遺伝子改変免疫不全マウス。
- NOD.Cg-PrkdcscidCd47tm1FplIl2rgtm1WjlTg(CD47)2Sz/Szマウスである、マクロファージおよび/またはマクロファージ抗ヒト赤血球活性を欠損している、遺伝子改変免疫不全マウス。
- 遺伝子改変免疫不全マウスであって、前記マウスが、単純ヘルペスウイルス1チミジンキナーゼをコードする導入遺伝子を含み、ヌクレオシドアナログと組み合わせると前記マウスのマクロファージを欠損させる単純ヘルペスウイルス1チミジンキナーゼタンパク質を発現する、前記遺伝子改変免疫不全マウス。
- 前記ヌクレオシドアナログが、ガンシクロビル、アシクロビルおよびその組み合わせから選択される、請求項6に記載の遺伝子改変免疫不全マウス。
- 前記遺伝子改変免疫不全マウスの前記ゲノムにおいてLyst遺伝子のエキソン5からの25bp配列:GAGCCGGTAGCTTTGGTTCAACGGA(配列番号1)の欠失を含む、請求項1に記載の遺伝子改変免疫不全マウス。
- ヒト赤血球をさらに含む、請求項1~8のいずれか一項に記載の遺伝子改変免疫不全マウス。
- ヒト造血細胞をさらに含む、請求項1~9のいずれか一項に記載の遺伝子改変免疫不全マウス。
- ヒト赤血球が感染因子に感染している、請求項9または10に記載の遺伝子改変免疫不全マウス。
- 前記感染因子が、プラスモディウム属寄生生物である、請求項11に記載の遺伝子改変免疫不全マウス。
- 前記感染因子が、熱帯熱マラリア原虫(Plasmodium falciparum)、卵形マラリア原虫(Plasmodium ovale)、三日熱マラリア原虫(Plasmodium vivax)、または四日熱マラリア原虫(Plasmodium malariae)である、請求項11または12に記載の遺伝子改変免疫不全マウス。
- 前記ヒト赤血球が、個々のヒトまたはヒト個体の集団に由来しており、前記個々のヒトまたはヒト個体の集団が鎌状赤血球貧血を有する、請求項9~13のいずれか一項に記載の遺伝子改変免疫不全マウス。
- 想定される治療剤の効果をアッセイする方法であって、
請求項9~14のいずれか一項に記載の遺伝子改変免疫不全マウスに、所定量の前記想定される治療剤を投与するステップ、および前記想定される治療剤の効果を測定するステップ
を包含する、方法。
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US201662373671P | 2016-08-11 | 2016-08-11 | |
US62/373,671 | 2016-08-11 | ||
PCT/US2017/046566 WO2018031920A1 (en) | 2016-08-11 | 2017-08-11 | Methods and compositions relating to improved human red blood cell survival in genetically modified immunodeficient non-human animals |
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EP (2) | EP4056031A1 (ja) |
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