JP2022512266A - ポリヌクレオチドシーケンシングに使用するための組成物 - Google Patents
ポリヌクレオチドシーケンシングに使用するための組成物 Download PDFInfo
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- JP2022512266A JP2022512266A JP2020572478A JP2020572478A JP2022512266A JP 2022512266 A JP2022512266 A JP 2022512266A JP 2020572478 A JP2020572478 A JP 2020572478A JP 2020572478 A JP2020572478 A JP 2020572478A JP 2022512266 A JP2022512266 A JP 2022512266A
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- polynucleotide
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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Abstract
Description
本開示は、とりわけ、ポリヌクレオチドのシーケンシングに関する。
テンプレートポリヌクレオチド鎖のシーケンシングは、サイクルごとに1つの検出可能なヌクレオチドがテンプレート鎖と相補的なコピー鎖に取り込まれるステップの複数のサイクルを通して起こり得る。検出可能なヌクレオチドは、通常、サイクルごとに複数の検出可能なヌクレオチドの取り込みを防ぐためにブロックされる。インキュベーション時間の後、洗浄ステップが、通常、実行されて取り込まれていない検出可能なヌクレオチドを除去する。次いで、コピー鎖に取り込まれた検出可能なヌクレオチドの同一性が決定される検出ステップを、実行し得る。次に、ブロッキング剤がコピー鎖に最後に取り込まれたヌクレオチドから除去され、検出可能な部分がコピー鎖に取り込まれた最後のヌクレオチドから切断またはマスキングされる、脱ブロッキングステップおよび切断またはマスキングステップが実行される。いくつかの例では、ブロッキング部分を除去するステップはまた、検出可能な部分も除去する。次いで、取り込みステップでブロックされた検出可能なヌクレオチドを導入することにより、このサイクルが繰り返される。
本開示は、とりわけ、検出ステップおよび切断後洗浄ステップの両方に単一の組成物を使用するポリヌクレオチドシーケンシング方法を記載する。同じ組成物が検出ステップおよび切断後洗浄ステップに使用される場合、シーケンシングプロセスで使用される組成物の数を減少し得、これは1以上の利点を提供し得る。例えば、試薬または組成物の数を減少することは、複数の組成物について適正製造基準および組成物または試薬の安定性を確保する負担を減少し得る。さらに、シーケンシング中のより少ない組成物の使用は、シーケンシング機器およびシーケンシング機器と共に使用される構成要素の複雑さを軽減し得、これは、機器および構成要素の信頼性を改善し得る。
ここで、本開示の主題の種々の実施形態をより詳細に参照し、そのいくつかの実施形態を添付の図面に示す。
・ScavScanで洗浄した後に実施するユニバーサルバッファー(「BB2」)洗浄の量を100uLから200uLに増加する;
・BB2バッファーのバッファー強度を普遍的に50mMから150mM(「BB2+」)に増加する;および
・走査ミックスを再製剤化する。
・ベースライン(BB7とBB2洗浄)
・ScavScan/2x BB2(ScavScanと2倍体積(ベースラインに対して)のBB2洗浄)
・BB2+(ベースラインとユニバーサル洗浄、BB2、150mM Trisを有するように改変)
・BB2++(ベースラインとユニバーサル洗浄、BB2、300mM Trisを有するように改変)
・ScavScan/BB2+(ScavScanとBB2+洗浄)
・ScavScan BB2 150mM Tris 2:ScavScan/BB2+の繰り返し
・DPPA/走査(10mM DPPAをScan Mix、VSMに追加)
・DPPA/BB2(10mM DPPAをBB2に追加)
・ベースライン(BB7とBB2洗浄)
・BB2+(BB7とユニバーサル洗浄、BB2、150mM Trisを有するように改変)
・ScavScan/BB2+(ScavScanとBB2+洗浄)
・DPPA(10mM DPPAをBB2、BB2洗浄に追加)
Claims (15)
- 以下を含むポリヌクレオチドシーケンシング方法:
(a)ブロック化標識化ヌクレオチドを、テンプレートポリヌクレオチド鎖の少なくとも一部と相補的なコピーポリヌクレオチド鎖の中へ取り込むこと;
(b)前記ブロック化標識化ヌクレオチドの同一性を、第1のバッファー組成物の存在下で検出すること;
(c)標識およびブロッキング部分を、コピー鎖の中へ取り込まれた前記ブロック化標識化ヌクレオチドから化学的に除去すること;
(d)化学的に除去された標識およびブロッキング部分を、前記コピー鎖から、前記第1のバッファー組成物を含む洗浄溶液で洗い流すこと、
であって、前記第1のバッファー組成物は、酸化防止剤およびスカベンジャー化合物を含む、
ポリヌクレオチドシーケンシング方法。 - ステップ(a)~(d)を、前記テンプレートポリヌクレオチド鎖の前記一部の配列が決定されるまで繰り返すことをさらに含む、請求項1に記載の方法。
- 前記スカベンジャー化合物が、ジスルフィド部分またはアジド部分を含む、請求項1または2に記載の方法。
- 前記スカベンジャー化合物が、ジスルフィド部分を含む、請求項3に記載の方法。
- 前記スカベンジャー化合物が、リポ酸または3,3’-ジチオジプロピオン酸(DDPA)である、請求項3に記載の方法。
- 前記標識およびブロッキング部分をコピーポリヌクレオチド鎖の中へ取り込まれた前記ブロック化標識化ヌクレオチドから除去することが、前記コピー鎖をtris(ヒドロキシメチル)ホスフィンと接触させることを含む、請求項1~5のいずれか一項に記載の方法。
- 前記第1のバッファー組成物が、アスコルビン酸塩、アセトバニロン、および6-ヒドロキシ-2,5,7,8-テトラメチルクロマン-2-カルボン酸からなる群から選択される酸化防止剤を含む、請求項1~6のいずれか一項に記載の方法。
- 前記テンプレートポリヌクレオチド鎖が、固体支持体と結合している、請求項1から7のいずれか一項に記載の方法。
- テンプレートポリヌクレオチドがフローセルと結合している、請求項8に記載の方法。
- シーケンシング装置と共に使用するためのカートリッジであって、前記カートリッジは、複数の組成物を含む複数のチャンバーを含み、各チャンバーは、単一の組成物を含み、前記組成物群は、以下からなる、カートリッジ:
(a)ブロック化標識化ヌクレオチドを、テンプレートポリヌクレオチド鎖の少なくとも一部と相補的なコピーポリヌクレオチド鎖の中へ取り込むための試薬;
(b)酸化防止剤およびスカベンジャーを含むバッファー組成物;
(c)標識およびブロッキング部分を、コピー鎖の中へ取り込まれた前記ブロック化標識化ヌクレオチドから化学的に除去するための試薬;および
(d)洗浄バッファー。 - シーケンシング装置と共に使用するためのキットであって、複数の組成物を含む複数のチャンバーを含み、各チャンバーは、単一の組成物を含み、前記組成物群は、以下からなる、キット:
(a)ブロック化標識化ヌクレオチドを、テンプレートポリヌクレオチド鎖の少なくとも一部と相補的なコピーポリヌクレオチド鎖の中へ取り込むための試薬;
(b)酸化防止剤およびスカベンジャーを含むバッファー組成物;
(c)標識およびブロッキング部分を、コピー鎖の中へ取り込まれた前記ブロック化標識化ヌクレオチドから化学的に除去するための試薬;および
(d)洗浄バッファー。 - 前記スカベンジャーが、ジスルフィド部分を含む、請求項10に記載のカートリッジまたは請求項12に記載のキット。
- 前記スカベンジャーが、リポ酸または3,3’-ジチオジプロピオン酸(DDPA)である、請求項10に記載のカートリッジまたは請求項11に記載のキット。
- 以下を含むポリヌクレオチドシーケンシング方法:
標識およびブロッキング部分を、テンプレートポリヌクレオチド鎖の少なくとも一部と相補的であるコピーポリヌクレオチド鎖の中へ取り込まれたブロック化標識化ヌクレオチドから除去すること;および
除去したラベルおよびブロッキング部分を、3,3’-ジチオジプロピオン酸(DDPA)を含む洗浄溶液でコピー鎖から洗い流すこと。 - 以下:
前記ブロック化標識化ヌクレオチドを化学的に除去する前に、コピー鎖の中へ取り込まれたブロック化標識化ヌクレオチドの同一性を検出すること、
をさらに含み、
前記ブロック化標識化ヌクレオチドの同一性を検出することが、第1のバッファー組成物の存在下で行われる、
請求項14に記載の方法。
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