JP2019536425A5 - - Google Patents

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JP2019536425A5
JP2019536425A5 JP2019506123A JP2019506123A JP2019536425A5 JP 2019536425 A5 JP2019536425 A5 JP 2019536425A5 JP 2019506123 A JP2019506123 A JP 2019506123A JP 2019506123 A JP2019506123 A JP 2019506123A JP 2019536425 A5 JP2019536425 A5 JP 2019536425A5
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  1. デオキシリボ核酸（ＤＮＡ）におけるデオキシアデノシンのアデニンを脱アミノ化することが可能なアデノシンデアミナーゼ。
  2. E. coli ＴａｄＡデアミナーゼ（ｅｃＴａｄＡ）またはS. aureus ＴａｄＡデアミナーゼ（ｓａＴａｄＡ）である、請求項１に記載のアデノシンデアミナーゼ。
  3. 配列番号１、８、９、３７１、３７２、３７３、３７４、または３７５のアミノ酸配列と少なくとも８０％、８５％、９０％、９５％、９８％、９９％、または９９．５％同一であるアミノ酸配列を含む、請求項１または２に記載のアデノシンデアミナーゼ。
  4. 配列番号１、８、９、３７１、３７２、３７３、３７４、または３７５のアミノ酸配列と少なくとも８５％または少なくとも９０％同一であるアミノ酸配列を含むが、配列番号１のアミノ酸配列の８、１７、１８、２３、３４、３６、４５、４８、５１、５６、５９、８４、８５、９４、９５、１０２、１０４、１０６、１０７、１０８、１１０、１１８、１２３、１２７、１３８、１４２、１４６、１４７、１４９、１５１、１５２、１５３、１５４、１５５、１５６、および１５７位から選択される位置、および配列番号８、９、３７１、３７２、３７３、３７４、および３７５における対応する位置の１以上の置換を除く、請求項１〜３のいずれか一項に記載のアデノシンデアミナーゼ。
  5. １以上の置換が、配列番号１のアミノ酸配列の２３、３６、４８、５１、８４、１０６、１０８、１２３、１４２、１４６、１４７、１５２、１５５、１５６、および１５７位から選択される位置、および配列番号８、９、３７１、３７２、３７３、３７４、および３７５における対応する位置のものである、請求項４に記載のアデノシンデアミナーゼ。
  6. １以上の置換が、配列番号１のアミノ酸配列のＷ２３Ｒ、Ｗ２３Ｌ、Ｈ３６Ｌ、Ｐ４８Ｓ、Ｐ４８Ａ、Ｒ５１Ｌ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ｓ１４６Ｃ、Ｄ１４７Ｙ、Ｒ１５２Ｐ、Ｅ１５５Ｖ、Ｉ１５６Ｆ、およびＫ１５７Ｎ、および配列番号８、９、３７１、３７２、３７３、３７４、および３７５における対応する置換からなる群から選択される置換である、請求項４に記載のアデノシンデアミナーゼ。
  7. １以上の置換が、配列番号１のアミノ酸配列の以下：
    （ｉ）Ｗ２３、Ｈ３６、Ｐ４８、Ｒ５１、Ｌ８４、Ａ１０６、Ｄ１０８、Ｈ１２３、Ａ１４２、Ｓ１４６、Ｄ１４７、Ｒ１５２、Ｅ１５５、Ｉ１５６、およびＫ１５７；
    （ｉｉ）Ｗ２３、Ｈ３６、Ｐ４８、Ｒ５１、Ｌ８４、Ａ１０６、Ｄ１０８、Ｈ１２３、Ｓ１４６、Ｄ１４７、Ｒ１５２、Ｅ１５５、Ｉ１５６、およびＫ１５７；
    （ｉｉｉ）Ｈ３６、Ｐ４８、Ｒ５１、Ｌ８４、Ａ１０６、Ｄ１０８、Ｈ１２３、Ａ１４２、Ｓ１４６、Ｄ１４７、Ｅ１５５、Ｉ１５６、およびＫ１５７；
    （ｉｖ）Ｈ３６、Ｐ４８、Ｒ５１、Ｌ８４、Ａ１０６、Ｄ１０８、Ｈ１２３、Ｓ１４６、Ｄ１４７、Ｅ１５５、Ｉ１５６、およびＫ１５７；
    （ｖ）Ｈ３６、Ｒ５１、Ｌ８４、Ａ１０６、Ｄ１０８、Ｈ１２３、Ｓ１４６、Ｄ１４７、Ｅ１５５、Ｉ１５６、およびＫ１５７；
    （ｖｉ）Ｌ８４、Ａ１０６、Ｄ１０８、Ｈ１２３、Ｄ１４７、Ｅ１５５、およびＩ１５６；
    （ｖｉｉ）Ａ１０６、Ｄ１０８、Ｄ１４７、およびＥ１５５；
    （ｖｉｉｉ）Ａ１０６、およびＤ１０８；および
    （ｉｘ）Ｄ１０８；
    の置換の群、または配列番号８、９、３７１、３７２、３７３、３７４、および３７５のいずれかにおける対応する置換の群
    のうちの１つを含む、請求項４に記載のアデノシンデアミナーゼ。
  8. １以上の置換が、配列番号１のアミノ酸配列の以下：
    （ｉ）Ｗ２３Ｌ、Ｈ３６Ｌ、Ｐ４８Ａ、Ｒ５１Ｌ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ｓ１４６Ｃ、Ｄ１４７Ｙ、Ｒ１５２Ｐ、Ｅ１５５Ｖ、Ｉ１５６Ｆ、およびＫ１５７Ｎ；
    （ｉｉ）Ｗ２３Ｒ、Ｈ３６Ｌ、Ｐ４８Ａ、Ｒ５１Ｌ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ｓ１４６Ｃ、Ｄ１４７Ｙ、Ｒ１５２Ｐ、Ｅ１５５Ｖ、Ｉ１５６Ｆ、およびＫ１５７Ｎ；
    （ｉｉｉ）Ｈ３６Ｌ、Ｐ４８Ｓ、Ｒ５１Ｌ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ｓ１４６Ｃ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、Ｉ１５６Ｆ、およびＫ１５７Ｎ；
    （ｉｖ）Ｈ３６Ｌ、Ｐ４８Ｓ、Ｒ５１Ｌ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ｓ１４６Ｃ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、Ｉ１５６Ｆ、およびＫ１５７Ｎ；
    （ｖ）Ｈ３６Ｌ、Ｒ５１Ｌ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ｓ１４６Ｃ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、Ｉ１５６Ｆ、およびＫ１５７Ｎ；
    （ｖｉ）Ｌ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｆ；
    （ｖｉｉ）Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｄ１４７Ｙ、およびＥ１５５Ｖ；
    （ｖｉｉｉ）Ａ１０６Ｖ、およびＤ１０８Ｎ；および
    （ｉｘ）Ｄ１０８Ｎ；
    の置換の群、または配列番号８、９、３７１、３７２、３７３、３７４、および３７５のいずれかにおける対応する置換の群
    のうちの１つを含む、請求項４に記載のアデノシンデアミナーゼ。
  9. アデノシンデアミナーゼのアミノ酸配列が、配列番号１におけるＤ１０８Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異を含み、Ｘが、Ｄ以外の任意のアミノ酸であり、例えば、Ｘが、Ｇ、Ｎ、Ｖ、Ａ、またはＹである、請求項１〜８のいずれか一項に記載のアデノシンデアミナーゼ。
  10. アデノシンデアミナーゼのアミノ酸配列が、配列番号１におけるＡ１０６Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異を含み、Ｘが、Ａ以外の任意のアミノ酸であり、例えば、Ｘが、Ｖ、Ｉ、またはＬである、請求項１〜９のいずれか一項に記載のアデノシンデアミナーゼ。
  11. 請求項１〜１０のいずれか一項に記載のアデノシンデアミナーゼであって、アデノシンデアミナーゼのアミノ酸配列が、
    ａ）配列番号１におけるＥ１５５Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｅ以外の任意のアミノ酸、例えば、Ｄ、Ｇ、またはＶである；または
    ｂ）配列番号１におけるＤ１４７Ｘ変異、または別のアデニンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｄ以外の任意のアミノ酸、例えば、ＹまたはＦである；または
    ｃ）配列番号１におけるＳ２Ａ、Ｈ８Ｙ、Ｉ４９Ｆ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ａ１０６Ｔ、Ｄ１０８Ｒ、Ｈ１２３Ｙ、Ｎ１２７Ｓ、Ｄ１４７Ｙ、Ｑ１５４Ｈ、Ｅ１５５Ｖ、Ｉ１５６Ｆ、およびＫ１６０Ｓ変異からなる群から選択される１以上の変異、または別のアデノシンデアミナーゼにおける１以上の対応する変異；または
    ｄ）配列番号１におけるＨ１５６Ｆ変異、または別のアデニンデアミナーゼにおける対応する変異；または
    ｅ）配列番号１におけるＥ２５Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｅ以外の任意のアミノ酸、例えば、Ｍ、Ｄ、Ａ、Ｒ、Ｖ、Ｓ、またはＹである；または
    ｆ）配列番号１におけるＲ２６Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｒ以外の任意のアミノ酸、例えば、Ｇ、Ｎ、Ｑ、Ｃ、Ｌ、またはＫである；または
    ｇ）配列番号１におけるＲ１０７Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｒ以外の任意のアミノ酸、例えば、Ｐ、Ｋ、Ａ、Ｎ、Ｗ、Ｈ、またはＳである；または
    ｈ）配列番号１におけるＡ１４２Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ａ以外の任意のアミノ酸、例えば、Ｎ、Ｄ、またはＧである；または
    ｉ）配列番号１におけるＡ１４３Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ａ以外の任意のアミノ酸、例えば、Ｄ、Ｇ、Ｅ、Ｌ、Ｗ、Ｍ、Ｓ、Ｑ、またはＲである；または
    ｊ）配列番号１におけるＨ３６Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｈ以外の任意のアミノ酸、例えば、Ｌである；または
    ｋ）配列番号１におけるＮ３７Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｎ以外の任意のアミノ酸、例えば、ＴまたはＳである；または
    ｌ）配列番号１におけるＰ４８Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｐ以外の任意のアミノ酸、例えば、Ｓ、Ｔ、Ａ、またはＬである；または
    ｍ）配列番号１におけるＲ５１Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｒ以外の任意のアミノ酸、例えば、ＨまたはＬである；または
    ｎ）配列番号１におけるＳ１４６Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｓ以外の任意のアミノ酸、例えば、ＲまたはＣである；または
    ｏ）配列番号１におけるＬ１５７Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｌ以外の任意のアミノ酸、例えば、Ｎである；または
    ｐ）配列番号１におけるＷ２３Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｗ以外の任意のアミノ酸、例えば、ＲまたはＬである；または
    ｑ）配列番号１におけるＲ１５２Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｒ以外の任意のアミノ酸、例えば、ＰまたはＨである、
    を含む、前記アデノシンデアミナーゼ。
  12. 請求項１〜１１のいずれか一項に記載のアデノシンデアミナーゼであって、アデノシンデアミナーゼのアミノ酸配列が、
    ａ）配列番号１におけるＡ１０６ＶおよびＤ１０８Ｎ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｂ）配列番号１におけるＲ１０７ＣおよびＤ１０８Ｎ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｃ）配列番号１におけるＨ８Ｙ、Ｄ１０８Ｎ、Ｎ１２７Ｓ、Ｄ１４７Ｙ、およびＱ１５４Ｈ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｄ）配列番号１におけるＨ８Ｙ、Ｒ２６Ｗ、Ｄ１０８Ｎ、Ｎ１２７Ｓ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｅ）配列番号１におけるＤ１０８Ｎ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｆ）配列番号１におけるＨ８Ｙ、Ｄ１０８Ｎ、Ｓ１２７Ｓ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｇ）配列番号１におけるＨ８Ｙ、Ｄ１０８Ｎ、Ｎ１２７Ｓ、Ｄ１４７Ｙ、およびＱ１５４Ｈ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｈ）配列番号１におけるＨ８Ｙ、Ｒ２６Ｗ、Ｄ１０８Ｎ、Ｎ１２７Ｓ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｉ）配列番号１におけるＡ１０６Ｖ、Ｄ１０８Ｎ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｊ）配列番号１におけるＤ１０８Ｑ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｋ）配列番号１におけるＤ１０８Ｍ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｌ）配列番号１におけるＤ１０８Ｌ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｍ）配列番号１におけるＤ１０８Ｋ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｎ）配列番号１におけるＤ１０８Ｉ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｏ）配列番号１におけるＤ１０８Ｆ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｐ）配列番号１におけるＡ１０６Ｖ、Ｄ１０８Ｎ、およびＤ１４７Ｙ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｑ）配列番号１におけるＡ１０６Ｖ、Ｄ１０８Ｍ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異
    を含む、前記アデノシンデアミナーゼ。
  13. 請求項１〜１１のいずれか一項に記載のアデノシンデアミナーゼであって、アデノシンデアミナーゼのアミノ酸配列が、
    ａ）配列番号１におけるＥ５９Ａ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｂ）配列番号１におけるＥ５９Ａ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｃ）配列番号１におけるＬ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｙ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｄ）配列番号１におけるＲ２６Ｇ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｒ１０７Ｈ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ａ１４３Ｄ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｆ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｅ）配列番号１におけるＥ２５Ｇ、Ｒ２６Ｇ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｒ１０７Ｈ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ａ１４３Ｄ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｆ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｆ）配列番号１におけるＲ２６Ｑ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｆ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｇ）配列番号１におけるＥ２５Ｍ、Ｒ２６Ｇ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｒ１０７Ｐ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ａ１４３Ｄ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｆ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｈ）配列番号１におけるＲ２６Ｃ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｒ１０７Ｈ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｆ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｉ）配列番号１におけるＬ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ａ１４３Ｌ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｆ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｊ）配列番号１におけるＲ２６Ｇ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｆ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｋ）配列番号１におけるＥ２５Ａ、Ｒ２６Ｇ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｒ１０７Ｎ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ａ１４３Ｅ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｆ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｌ）配列番号１におけるＥ２５Ｄ、Ｒ２６Ｇ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｒ１０７Ｋ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ａ１４２Ｎ、Ａ１４３Ｇ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、およびＩ１５６Ｆ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｍ）配列番号１におけるＬ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、Ｉ１５６Ｆ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｎ）配列番号１におけるＡ１０６Ｖ、Ｄ１０８Ｎ、Ａ１４２Ｎ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｏ）配列番号１におけるＲ２６Ｇ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ａ１４２Ｎ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｐ）配列番号１におけるＥ２５Ｄ、Ｒ２６Ｇ、Ａ１０６Ｖ、Ｒ１０７Ｋ、Ｄ１０８Ｎ、Ａ１４２Ｎ、Ａ１４３Ｇ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｑ）配列番号１におけるＲ２６Ｇ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｒ１０７Ｈ、Ａ１４２Ｎ、Ａ１４３Ｄ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｒ）配列番号１におけるＥ２５Ｄ、Ｒ２６Ｇ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ａ１４２Ｎ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｓ）配列番号１におけるＡ１０６Ｖ、Ｒ１０７Ｋ、Ｄ１０８Ｎ、Ａ１４２Ｎ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｔ）配列番号１におけるＡ１０６Ｖ、Ｄ１０８Ｎ、Ａ１４２Ｎ、Ａ１４３Ｇ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｕ）配列番号１におけるＡ１０６Ｖ、Ｄ１０８Ｎ、Ａ１４２Ｎ、Ａ１４３Ｌ、Ｄ１４７Ｙ、およびＥ１５５Ｖ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｖ）配列番号１におけるＨ３６Ｌ、Ｒ５１Ｌ、Ｌ８４Ｆ、Ａ１０６Ｖ、Ｄ１０８Ｎ、Ｈ１２３Ｙ、Ｓ１４６Ｃ、Ｄ１４７Ｙ、Ｅ１５５Ｖ、Ｉ１５６Ｆ、およびＫ１５７Ｎ変異、または別のアデノシンデアミナーゼにおける対応する変異
    を含む、前記アデノシンデアミナーゼ。
  14. 請求項３に記載のアデノシンデアミナーゼであって、アデノシンデアミナーゼのアミノ酸配列が、
    ａ）配列番号８におけるＤ１０７Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｄ以外の任意のアミノ酸、例えば、Ａである；または
    ｂ）配列番号８におけるＤ１０８Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｄ以外の任意のアミノ酸、例えば、Ｎである；または
    ｃ）配列番号８におけるＧ２６Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｇ以外の任意のアミノ酸、例えば、Ｐである；または
    ｄ）配列番号８におけるＳ１４２Ｘ変異、または別のアデノシンデアミナーゼにおける対応する変異、ここで、Ｘは、Ｓ以外の任意のアミノ酸、例えば、Ａである；または
    ｅ）配列番号８におけるＤ１０７ＡおよびＤ１０８Ｎ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｆ）配列番号８におけるＤ１０７Ａ、Ｄ１０８Ｎ、およびＧ２６Ｐ変異、または別のアデノシンデアミナーゼにおける対応する変異；または
    ｇ）配列番号８におけるＤ１０７Ａ、Ｄ１０８Ｎ、Ｇ２６Ｐ、およびＳ１４２Ａ変異；または別のアデノシンデアミナーゼにおける対応する変異
    を含む、前記アデノシンデアミナーゼ。
  15. アデノシンデアミナーゼのアミノ酸配列が、配列番号６４〜８４、４２０〜４３７、または６７２〜６８４のいずれか１つと少なくとも８５％、９０％、９５％、９８％、９９％、または９９．５％同一であるアミノ酸配列を含む、請求項１または２に記載のアデノシンデアミナーゼ。
  16. 塩基除去修復の阻害剤にカップリングされた、核酸誘導型アデノシンデアミナーゼ。
  17. （ｉ）核酸プログラム可能なＤＮＡ結合蛋白質（ｎａｐＤＮＡｂｐ）ドメイン、および（ｉｉ）請求項１〜１５のいずれか一項に記載のアデノシンデアミナーゼまたは請求項１６に記載の核酸誘導型アデノシンデアミナーゼを含むアデノシンデアミナーゼドメインを含む、融合蛋白質。
  18. ｎａｐＤＮＡｂｐドメインが、Ｃａｓ９ドメイン、Ｃｐｆ１ドメイン、ＣａｓＸドメイン、ＣａｓＹドメイン、Ｃ２ｃ１ドメイン、Ｃ２ｃ２ドメイン、またはＣ２ｃ３ドメインである、請求項１７に記載の融合蛋白質。
  19. Ｃａｓ９ドメインが、ヌクレアーゼ不活性型Ｃａｓ９（ｄＣａｓ９）、Ｃａｓ９ニッカーゼ（ｎＣａｓ９）、またはヌクレアーゼ活性型Ｃａｓ９である、請求項１８に記載の融合蛋白質。
  20. （ｉｉｉ）塩基修復（ＩＢＲ）の阻害剤をさらに含む、請求項１７〜１９のいずれか一項に記載の融合蛋白質。
  21. アデノシンデアミナーゼドメインが、リンカーを介してｎａｐＤＮＡｂｐドメインに融合されている、請求項１７〜２０のいずれか一項に記載の融合蛋白質。
  22. １以上の核局在配列（ＮＬＳ）をさらに含む、請求項１７〜２１のいずれか一項に記載の融合蛋白質。
  23. 請求項２２に記載の融合蛋白質であって、
    ｎａｐＤＮＡｂｐおよびＮＬＳが、アミノ酸配列：ＳＧＧＳ（配列番号３７）、ＳＧＳＥＴＰＧＴＳＥＳＡＴＰＥＳ（配列番号１０）、ＳＧＧＳＳＧＧＳＳＧＳＥＴＰＧＴＳＥＳＡＴＰＥＳＳＧＧＳＳＧＧＳ（配列番号３８５）、またはＧＧＳＧＧＳＰＧＳＰＡＧＳＰＴＳＴＥＥＧＴＳＥＳＡＴＰＥＳＧＰＧＴＳＴＥＰＳＥＧＳＡＰＧＳＰＡＧＳＰＴＳＴＥＥＧＴＳＴＥＰＳＥＧＳＡＰＧＴＳＴＥＰＳＥＧＳＡＰＧＴＳＥＳＡＴＰＥＳＧＰＧＳＥＰＡＴＳＧＧＳＧＧＳ（配列番号３８６）を含むリンカーを介して融合されている、
    ｎａｐＤＮＡｂｐおよびＩＢＲが、アミノ酸配列：ＳＧＧＳ（配列番号３７）、ＳＧＳＥＴＰＧＴＳＥＳＡＴＰＥＳ（配列番号１０）、ＳＧＧＳＳＧＧＳＳＧＳＥＴＰＧＴＳＥＳＡＴＰＥＳＳＧＧＳＳＧＧＳ（配列番号３８５）、またはＧＧＳＧＧＳＰＧＳＰＡＧＳＰＴＳＴＥＥＧＴＳＥＳＡＴＰＥＳＧＰＧＴＳＴＥＰＳＥＧＳＡＰＧＳＰＡＧＳＰＴＳＴＥＥＧＴＳＴＥＰＳＥＧＳＡＰＧＴＳＴＥＰＳＥＧＳＡＰＧＴＳＥＳＡＴＰＥＳＧＰＧＳＥＰＡＴＳＧＧＳＧＧＳ（配列番号３８６）を含むリンカーを介して融合されている、および／または
    ＩＢＲおよびＮＬＳが、アミノ酸配列：ＳＧＧＳ（配列番号３７）、ＳＧＳＥＴＰＧＴＳＥＳＡＴＰＥＳ（配列番号１０）、ＳＧＧＳＳＧＧＳＳＧＳＥＴＰＧＴＳＥＳＡＴＰＥＳＳＧＧＳＳＧＧＳ（配列番号３８５）、またはＧＧＳＧＧＳＰＧＳＰＡＧＳＰＴＳＴＥＥＧＴＳＥＳＡＴＰＥＳＧＰＧＴＳＴＥＰＳＥＧＳＡＰＧＳＰＡＧＳＰＴＳＴＥＥＧＴＳＴＥＰＳＥＧＳＡＰＧＴＳＴＥＰＳＥＧＳＡＰＧＴＳＥＳＡＴＰＥＳＧＰＧＳＥＰＡＴＳＧＧＳＧＧＳ（配列番号３８６）を含むリンカーを介して融合されている、
    前記融合蛋白質。
  24. 第２のアデノシンデアミナーゼドメインをさらに含む、請求項１７〜２３のいずれか一項に記載の融合蛋白質。
  25. 以下の構造：
    ［第１のアデノシンデアミナーゼ］−［第２のアデノシンデアミナーゼ］−［ｎａｐＤＮＡｂｐドメイン］；
    ［第１のアデノシンデアミナーゼ］−［ｎａｐＤＮＡｂｐドメイン］−［第２のアデノシンデアミナーゼ］；
    ［ｎａｐＤＮＡｂｐドメイン］−［第１のアデノシンデアミナーゼ］−［第２のアデノシンデアミナーゼ］；
    ［第１のアデノシンデアミナーゼ］−［第２のアデノシンデアミナーゼ］−［ｎａｐＤＮＡｂｐドメイン］−［ＮＬＳ］；
    ［第１のアデノシンデアミナーゼ］−［第２のアデノシンデアミナーゼ］−［ｎａｐＤＮＡｂｐドメイン］−［ＩＢＲ］；または
    ［第１のアデノシンデアミナーゼ］−［第２のアデノシンデアミナーゼ］−［ｎａｐＤＮＡｂｐドメイン］−［ＩＢＲ］−［ＮＬＳ］、
    ここで、ＩＢＲは塩基除去修復の阻害剤であり、および構造における各「］−［」は任意のリンカーの存在を示す、
    を含む、請求項２４に記載の融合蛋白質。
  26. 配列番号１１〜２８、３８７〜３８８、４４０、または６９１〜７０６のアミノ酸配列のいずれか１つと少なくとも８５％、少なくとも９０％、少なくとも９５％、少なくとも９８％、少なくとも９９％、または少なくとも９９．５％同一であるアミノ酸配列を含む、請求項１７〜２５のいずれか一項に記載の融合蛋白質。
  27. 配列番号１１〜２８、３８７〜３８８、４４０、または６９１〜７０６のアミノ酸配列のいずれか１つを含むアミノ酸配列を含む、請求項１７〜２６のいずれか一項に記載の融合蛋白質。
  28. 請求項１７〜２７のいずれか一項に記載の融合蛋白質および融合蛋白質の核酸プログラム可能なＤＮＡ結合蛋白質（ｎａｐＤＮＡｂｐ）ドメインに結合したガイドＲＮＡを含む複合体であって、ガイドＲＮＡが、標的配列に対して相補的である少なくとも１０ヌクレオチドの一続きの配列を含む、前記複合体。
  29. 標的配列が、原核生物または真核生物のゲノム中にある、請求項２８に記載の複合体。
  30. 標的核酸配列を、請求項１７〜２７のいずれか一項に記載の融合蛋白質およびガイドＲＮＡ、または請求項２８または２９に記載の複合体と接触させることを含む、標的核酸配列の核酸塩基を編集するためのインビトロまたはエクスビボの方法であって、ガイドＲＮＡが１５〜１００ヌクレオチド長であり、および標的核酸配列に対して相補的である少なくとも１０ヌクレオチドの一続きの配列を含む、前記方法。
  31. 標的核酸配列がＤＮＡ配列を含む、請求項３０に記載の方法。
  32. 標的核酸配列が、疾患または異常に関連する点変異を含む、請求項３０または３１に記載の方法。
  33. 標的核酸配列が、疾患または異常に関連するＧからＡへの点変異を含み；および変異Ａ塩基の脱アミノ化が、疾患または異常に関連しない配列をもたらす、請求項３０〜３２のいずれか一項に記載の方法。
  34. 標的配列が、疾患または異常に関連するＣからＴへの点変異を含み；およびＣからＴへの点変異のＴ塩基に相補的であるＡ塩基の脱アミノ化が、疾患または異常に関連しない配列をもたらす、請求項３０〜３２のいずれか一項に記載の方法。
  35. Ａ塩基を脱アミノ化する効率が、少なくとも１０％、１５％、２０％、２５％、３０％、３５％、４０％、４５％、５０％、６０％、７０％、８０％、９０％、９５％、または９８％である、請求項３０〜３４のいずれか一項に記載の方法。
  36. 点変異がコドン中にあり、および接触させるステップが、野生型コドンと比較して変異コドンによってコードされるアミノ酸の変化をもたらす、または終止コドンの除去をもたらす、請求項３０〜３５のいずれか一項に記載の方法。
  37. 接触させるステップが、スプライス部位の導入をもたらす、スプライス部位の除去をもたらす、遺伝子プロモーターにおける変異の導入をもたらす、または遺伝子リプレッサーにおける変異の導入をもたらす、請求項３０〜３５のいずれか一項に記載の方法。
  38. ２０％、１９％、１８％、１６％、１４％、１２％、１０％、８％、６％、４％、２％、１％、０．５％、０．２％、または０．１％未満のインデル形成を引き起こす、請求項３０〜３７のいずれか一項に記載の方法。
  39. 請求項１〜１５のいずれか一項に記載のアデノシンデアミナーゼ、請求項１６に記載の核酸誘導型アデノシンデアミナーゼ、または請求項１７〜２７のいずれか一項に記載の融合蛋白質をコードする、ポリヌクレオチド。
  40. 請求項３９に記載のポリヌクレオチドを含むベクターであって、ポリヌクレオチドの発現を駆動する異種プロモーターを含む、前記ベクター。
  41. 請求項１〜１５のいずれか一項に記載のアデノシンデアミナーゼ、請求項１６に記載の核酸誘導型アデノシンデアミナーゼ、請求項１７〜２７のいずれか一項に記載の融合蛋白質、請求項２８または２９に記載の複合体、請求項３９に記載のポリヌクレオチド、または請求項４０に記載のベクターを含む、細胞。
  42. 請求項１７〜２７のいずれか一項に記載の融合蛋白質、請求項２８または２９に記載の複合体、請求項３９に記載のポリヌクレオチド、または請求項４０に記載のベクターを含む、医薬組成物。
  43. 医薬としての使用のための、請求項１７〜２７のいずれか一項に記載の融合蛋白質、請求項２８または２９に記載の複合体、請求項３９に記載のポリヌクレオチド、請求項４０に記載のベクター、請求項４１に記載の細胞、または請求項４２に記載の医薬組成物。
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