JP2019520844A5 - - Google Patents

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JP2019520844A5
JP2019520844A5 JP2019502559A JP2019502559A JP2019520844A5 JP 2019520844 A5 JP2019520844 A5 JP 2019520844A5 JP 2019502559 A JP2019502559 A JP 2019502559A JP 2019502559 A JP2019502559 A JP 2019502559A JP 2019520844 A5 JP2019520844 A5 JP 2019520844A5
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cells
dna
cell
oligo
sequence
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Priority claimed from PCT/IB2017/054446 external-priority patent/WO2018015936A2/en
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Claims (15)

  1. （a）DNAオリゴと（b）DNA消化作用物質と（c）キャップ形成および/またはポリアデニル化されているターゲティングRNAとを含む組成物を、エレクトロポレーションにより細胞にトランスフェクトする工程
    を含む、該細胞における標的ゲノムDNA領域の部位特異的な配列改変のための方法であって、
    該DNAオリゴが、
    （i）該標的ゲノムDNA領域に相同なDNA配列を含む相同領域と、
    （ii）配列改変領域と
    を含み、かつ
    該標的ゲノムDNA領域においてゲノムDNA配列が特異的に改変される、方法。
  2. エレクトロポレーションが、フローエレクトロポレーションデバイスを用いるフローエレクトロポレーションである、請求項1に記載の方法。
  3. 前記DNA消化作用物質がヌクレアーゼである、または、前記DNA消化作用物質がCas9を含むヌクレアーゼである、請求項1〜2のいずれか一項に記載の方法。
  4. 前記ヌクレアーゼが部位特異的なヌクレアーゼである、かつ／または、前記ターゲティングRNAがガイドRNAを含む、請求項1〜3のいずれか一項に記載の方法。
  5. 前記オリゴが一本鎖である、請求項1〜4のいずれか一項に記載の方法。
  6. 前記DNAオリゴが10個超の核酸である、前記DNAオリゴが10〜800個の核酸である、前記DNAオリゴが10〜600個の核酸である、前記DNAオリゴが10〜200個の核酸である、前記DNAオリゴが10〜100個の核酸である、または、前記DNAオリゴが10〜50個の核酸である、請求項1〜5のいずれか一項に記載の方法。
  7. 前記組成物中の前記DNAオリゴの濃度が10μg/mLを上回る、前記組成物中の前記DNAオリゴの濃度が約10μg/mL〜約500μg/mLである、前記組成物中の前記DNAオリゴの濃度が約35μg/mL〜約300μg/mLである、もしくは、前記組成物中の前記DNAオリゴの濃度が約35μg/mL〜約200μg/mLである；かつ／または
    前記組成物が非ウイルス性である；かつ／または
    前記細胞が哺乳動物細胞である、前記細胞がヒト細胞である、前記細胞が線維芽細胞である、前記細胞が哺乳動物由来の末梢血リンパ球である、前記細胞が哺乳動物由来の増殖したT細胞である、前記細胞が哺乳動物由来の初代細胞である、前記細胞が幹細胞である、前記細胞が造血幹細胞である、もしくは、前記細胞が間葉系幹細胞である、
    請求項1〜6のいずれか一項に記載の方法。
  8. 前記ゲノムDNA配列が疾患関連遺伝子を含む、もしくは、前記ゲノムDNA配列が慢性肉芽腫性疾患関連遺伝子を含む；かつ／または
    前記ゲノムDNA配列がgp91phox遺伝子を含む、請求項1〜7のいずれか一項に記載の方法。
  9. 前記ゲノムDNA配列がHBB遺伝子を含む、かつ／または、前記配列改変が前記ゲノムDNAの修正であり、該修正により前記HBB遺伝子の6番目のコドンがグルタミン酸コドンに改変される、請求項1〜8のいずれか一項に記載の方法。
  10. 前記オリゴが、核酸少なくとも10個の相同配列を含む、前記オリゴが、核酸少なくとも20個の相同配列を含む、もしくは、前記オリゴが、核酸少なくとも30個の相同配列を含む；かつ／または
    前記配列改変の効率が3%超である、前記配列改変の効率が5%超である、もしくは、前記配列改変の効率が10%超である；かつ／または
    前記エレクトロポレーション後の細胞生存率が少なくとも30%である、前記エレクトロポレーション後の細胞生存率が少なくとも40%である、もしくは、前記エレクトロポレーション後の細胞生存率が少なくとも50%である；かつ／または
    前記DNA配列改変が、1つまたは複数の終止コドンである；かつ／または
    前記組成物が、異なる相同配列を有する2つまたはそれ以上のDNAオリゴを含む、前記組成物が、2つまたはそれ以上のDNA消化作用物質を含む、および／もしくは、前記組成物が、2つまたはそれ以上の部位特異的なDNA消化作用物質を含み、該DNA消化作用物質が、異なるゲノム部位を標的にする；かつ／または
    前記配列改変により前記ゲノム配列の1塩基対または複数の塩基対が変化する、前記配列改変により前記ゲノム配列の1塩基対または複数の塩基対が付加される、もしくは、前記配列改変により前記ゲノム配列の1塩基対または複数の塩基対が欠失する、
    請求項1〜9のいずれか一項に記載の方法。
  11. 前記細胞が患者から単離された細胞である；かつ／または
    前記細胞が凍結保存されている、前記細胞が前記細胞のトランスフェクション前1週間以内の時期に前記患者から単離されている、もしくは、前記細胞が前記細胞のトランスフェクション前1日以内の時期に前記患者から単離されている、かつ／または
    前記細胞が凍結されていない単離された細胞である；かつ／または
    前記細胞が、2つまたはそれ以上の異なる細胞型を含む単離された細胞である、もしくは、前記細胞が、多能性に関する異なる段階における2つまたはそれ以上の細胞型を含む単離された細胞である；かつ／または
    前記配列改変の効率が3%超である、前記配列改変の効率が5%超である、もしくは、前記配列改変の効率が10%超である、
    請求項1〜10のいずれか一項に記載の方法。
  12. 前記エレクトロポレーション後の細胞生存率が少なくとも30%である、前記エレクトロポレーション後の細胞生存率が少なくとも40%である、もしくは、前記エレクトロポレーション後の細胞生存率が少なくとも50%である；かつ／または
    前記細胞が対象の骨髄から単離されている；かつ／または
    前記細胞が幹細胞を含む、前記細胞が造血幹細胞を含む幹細胞を含む、もしくは、前記細胞が細胞表面マーカーCD34+を含む幹細胞を含む、
    請求項1〜11のいずれか一項に記載の方法。
  13. 前記DNA配列改変を有するクローン細胞を産生するために、単離および選択されたクローン細胞を増殖させる工程をさらに含む；かつ／または
    前記細胞が大規模製造のために増殖される、前記細胞が1L超の体積で増殖される、もしくは、前記細胞が3Lまたはそれ以上の体積で増殖される；かつ／または
    前記細胞が無血清培地中で培養される；かつ／または
    前記配列改変について前記細胞をスクリーニングする工程をさらに含む；かつ／または
    トランスフェクトされた細胞を凍結させる工程をさらに含む、かつ／または
    以前に凍結させたトランスフェクトされた細胞を増殖させる工程をさらに含む、
    請求項1〜12のいずれか一項に記載の方法。
  14. 請求項1〜13のいずれか一項に記載の方法を使用して産生された、エレクトロポレーションされた細胞。
  15. 請求項14に記載のエレクトロポレーションされた細胞の有効量を含む、疾患もしくは状態を有するかまたは疾患もしくは状態を有することが疑われる対象の処置に使用するための組成物。
JP2019502559A 2016-07-21 2017-07-21 ゲノムｄｎａを改変するための方法および組成物 Pending JP2019520844A (ja)

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CN (1) CN109844103A (ja)
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