JP2023055884A - 改善された免疫細胞療法のためのnk阻害物質遺伝子の標的指向遺伝子組み込み - Google Patents
改善された免疫細胞療法のためのnk阻害物質遺伝子の標的指向遺伝子組み込み Download PDFInfo
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Abstract
Description
本発明は、適応性細胞免疫療法の分野に属する。これは、腫瘍などの免疫耐性を発生する病状に対する初代免疫細胞の機能性を増強し、それによってこれらの免疫細胞の治療的可能性を改善することを目標にする。特に、本発明の方法は、患者のNK細胞による攻撃に起因する同種異系T細胞の拒絶を防止し、特にそれらがドナーに由来する場合に該T細胞の移植を支持するための、NK阻害物質をコードする外来性コード配列の遺伝的挿入を提供する。これらの外来性コード配列は、より詳細には、免疫細胞活性化時、腫瘍微小環境もしくは命を脅かす炎症状態上で上方制御される内在性遺伝子プロモーター、または免疫細胞活性化に対して非感受性であるもしくはプロモーターの転写制御下の細胞ゲノムに、より具体的にはβ2m遺伝子座に挿入される。本発明はさらに、前記特定の遺伝子座でそのような標的指向挿入を行うための、配列特異的エンドヌクレアーゼ試薬およびドナーDNAベクター、例えばAAVベクターも提供する。本発明の方法は、細胞療法における操作された初代免疫細胞の効率的な使用のために、それらの治療的可能性および安全性を改善することに寄与する。
造血細胞系列を含む初代免疫細胞集団の有効な臨床応用が、ある範囲の病状、特にHIV感染症および白血病に対して、10年間にわたって多数の臨床試験によって確立されている(Tristen S.J. et al. (2011) Treating cancer with genetically engineered T cells. Trends in Biotechnology. 29(11):550-557(非特許文献1))。
[本発明1001]
細胞免疫療法用の操作された初代免疫細胞を調製するための方法であって、
T細胞を含む細胞の集団を提供する工程;
該T細胞のある割合中に、
(i)少なくとも1種類のNK細胞阻害物質をコードするように、選択された内在性遺伝子座に組み込まれる外来性ポリヌクレオチド配列を含む、少なくとも1種類の核酸;
(ii)該選択された内在性遺伝子座を特異的に標的とする、少なくとも1種類の配列特異的試薬
を導入する工程
を含み、該外来性ポリヌクレオチド配列が、該内在性遺伝子座中への標的指向遺伝子組込みによって挿入される、前記方法。
[本発明1002]
前記配列特異的試薬がヌクレアーゼである、本発明1001の方法。
[本発明1003]
前記標的指向遺伝子組込みが、前記免疫細胞中への相同組換えまたはNHEJによって作動される、本発明1001または1002の方法。
[本発明1004]
前記外来性ポリヌクレオチド配列が、前記遺伝子座に存在する内在性プロモーターの転写制御下に組み込まれる、本発明1001~1003のいずれかの方法。
[本発明1005]
前記内在性遺伝子座が、MHC I構成要素、例えばβ2mを発現する遺伝子座である、本発明1004の方法。
[本発明1006]
前記外来性配列の前記挿入が、前記内在性遺伝子座でのβ2m発現を不活性化する、本発明1005の方法。
[本発明1007]
前記内在性プロモーターが、免疫細胞活性化の間に活性を有しているように選択される、本発明1001~1004のいずれかの方法。
[本発明1008]
前記内在性遺伝子座の前記内在性プロモーターが、T細胞活性化に対して応答性であり、例えば表6から選択される1つである、本発明1001~1007のいずれかの方法。
[本発明1009]
前記T細胞がキメラ抗原受容体(CAR)を与えられている、本発明1001~1008のいずれかの方法。
[本発明1010]
前記キメラ抗原受容体(CAR)をコードする外来性配列が、TCR遺伝子座に組み込まれる、本発明1009の方法。
[本発明1011]
前記キメラ抗原受容体(CAR)をコードする前記外来性配列が、内在性TCR配列の発現を阻止する、本発明1010の方法。
[本発明1012]
前記内在性遺伝子座での前記内在性プロモーターの活性が、前記キメラ抗原受容体(CAR)を通した前記T細胞の活性化に対して応答性である、本発明1009~1011のいずれかの方法。
[本発明1013]
前記特異的エンドヌクレアーゼ試薬が、RNAもしくはDNAガイドエンドヌクレアーゼ、例えばCas9もしくはCpf1、RNAもしくはDNAガイド、TALエンドヌクレアーゼ、Znフィンガーヌクレアーゼ、ホーミングエンドヌクレアーゼ、またはそれらの任意の組み合わせから選択される、本発明1001~1012のいずれかの方法。
[本発明1014]
NK阻害物質をコードする前記外来性配列が、非多型性クラスI分子、例えば、HLA-GもしくはHLA-E、またはその重鎖エピトープを含むその断片をコードする配列を好ましくは含む、本発明1001~1013のいずれかの方法。
[本発明1015]
前記外来性配列が、β2m内在性遺伝子座に組み込まれた場合に、その断片のHLA-EまたはHLA-Gとβ2m断片との融合物の発現を結果としてもたらす、本発明1005~1014のいずれかの方法。
[本発明1016]
その断片のHLA-EまたはHLA-Gとβ2m断片との前記融合物が、HLA-EまたはHLA-Gの二量体または三量体の発現を結果としてもたらす、本発明1015の方法。
[本発明1017]
NK阻害物質をコードする前記外来性配列が、ウイルスエバシンまたはそのエピトープを含む断片、例えばUL16(ULBP1とも呼ばれる‐Uniprot参照番号Q9BZM6)由来のものをコードする配列を好ましくは含む、本発明1001~1013のいずれかの方法。
[本発明1018]
前記T細胞が、初代細胞、好ましくはヒト初代T細胞である、本発明1001~1017のいずれかの方法。
[本発明1019]
本発明1001~1018のいずれかの方法によって取得可能である、操作されたT細胞。
[本発明1020]
内在性遺伝子プロモーターの転写制御下に組み込まれている、NK阻害物質をコードする外来性配列を含む、操作されたT細胞。
[本発明1021]
前記内在性遺伝子プロモーターが、表6に列挙される1つの遺伝子座で選択される、本発明1019または1020のいずれかの操作されたT細胞。
[本発明1022]
NK阻害物質をコードする前記外来性配列が、β2m遺伝子座に組み込まれている、本発明1019~1021のいずれかの操作されたT細胞。
[本発明1023]
前記T細胞がキメラ抗原受容体を与えられている、本発明1019~1022のいずれかの操作されたT細胞。
[本発明1024]
遺伝子型[TCR]陰性[β2m]陰性を有する、本発明1023の操作されたT細胞。
[本発明1025]
前記CARをコードする外来性配列が、TCR遺伝子座に組み込まれている、本発明1023または1024の操作されたT細胞。
[本発明1026]
前記T細胞が初代細胞である、本発明1019~1025のいずれかの操作されたT細胞。
[本発明1027]
がんまたは感染症の処置についてのその使用のための、本発明1019~1026のいずれかの操作されたT細胞。
[本発明1028]
少なくとも30%、好ましくは50%、より好ましくは80%の、本発明1019~1027のいずれかの操作されたT細胞を含む、治療上有効な免疫細胞の集団。
[本発明1029]
少なくとも30%、好ましくは50%、より好ましくは80%の細胞が、ドナー、好ましくは1人の単一ドナーを起源とする、本発明1028の治療上有効な免疫細胞の集団。
[本発明1030]
50%超の前記免疫細胞が、TCR陰性T細胞である、本発明1029の初代免疫細胞の集団。
[本発明1031]
50%超の前記免疫細胞が、CAR陽性細胞である、本発明1028~1030のいずれかの初代免疫細胞の集団。
[本発明1032]
本発明1028~1031のいずれかの操作された免疫細胞集団を含む、薬学的組成物。
[本発明1033]
以下の工程を含む、その必要がある患者を処置するための方法:
本発明1028~1032のいずれかの操作された初代免疫細胞の集団を調製する工程;
任意で、該操作された初代免疫細胞を精製または選別する工程;
該操作された初代免疫細胞の集団を、該細胞の該患者中への注入時または注入後に活性化する工程。
[本発明1034]
前記患者が、がんについて処置される、本発明1033の方法。
[本発明1035]
前記患者が、感染症について処置される、本発明1033の方法。
[本発明1036]
少なくとも以下の工程を含む、T細胞において発現可能なNK阻害物質をコードする適切な配列を特定するための方法:
TCRおよびβ2mの発現が両方とも抑えられているおよび/または不活性化されているT細胞を提供する工程;
推定のNK阻害物質をコードする候補配列を、該T細胞における内在性プロモーターの制御下の内在性遺伝子座に組み込む工程;
結果として生じた操作されたT細胞を、NK細胞の存在下で培養する工程。
[本発明1037]
少なくとも以下の工程を含む、T細胞において発現可能なNK阻害物質をコードする適切な配列を特定するための方法:
TCR発現が抑えられているかまたは不活性化されているT細胞を提供する工程;
推定のNK阻害物質をコードする候補配列をβ2m遺伝子座に組み込むことによって、該T細胞においてβ2m発現を不活性化する工程であって、該推定のNK阻害物質の発現が、該β2m遺伝子座の内在性プロモーターの転写制御下に置かれる、工程;
結果として生じた操作されたT細胞を、NK細胞の存在下で培養する工程。
[本発明1038]
前記T細胞にキメラ抗原受容体を与える工程
をさらに含む、本発明1036または1037の方法。
[本発明1039]
前記結果として生じた操作されたT細胞の生存を、前記候補配列を発現しない同じものと比較する工程;
任意で、NK細胞に対してより耐性である操作された細胞を選択する工程
をさらに含む、本発明1036~1038のいずれかの方法。
(表2)天然起源および人工起源由来のFPポリペプチドのアミノ酸配列。
(表3)本発明による外来性コード配列を挿入することによって有利に改変または不活性化することができる、免疫細胞阻害経路に関与する遺伝子のリスト。
(表4)実施例1において言及される配列。
(表5)実施例2および3において言及される配列。
(表6)免疫細胞の治療的可能性を改善するために、遺伝子標的指向挿入が本発明に従って探求される、T細胞活性化時に上方制御されるヒト遺伝子(CAR活性化感受性プロモーター)のリスト。
(表7)免疫細胞活性化の間に絶え間なく転写される(T細胞活性化に依存的または非依存的である)遺伝子の選択。
(表8)T細胞活性化時に一過性に上方制御される遺伝子の選択。
(表9)T細胞活性化時に24時間超にわたって上方制御される遺伝子の選択。
(表10)免疫細胞活性化時に下方制御される遺伝子の選択。
(表11)T細胞活性化時に無変化である遺伝子(安全港遺伝子標的指向組込み遺伝子座)の選択。
(表12)本発明の通りの外来性コード配列の遺伝子組込みに有用な、(複数の腫瘍から集計された)腫瘍消耗浸潤リンパ球において上方制御される遺伝子座のリスト。
(表13)本発明の通りの外来性コード配列の遺伝子組込みに有用な、低酸素腫瘍状態において上方制御される遺伝子座のリスト。
本明細書において具体的に定義されない限り、本明細書において用いられるすべての技術用語および科学用語は、遺伝子治療、生化学、遺伝学、および分子生物学の分野における当業者によって一般的に理解されるものと同じ意味を有する。
ポリヌクレオチド配列特異的試薬、例えば低頻度切断エンドヌクレアーゼを用いた遺伝子編集技法は、初代細胞中への遺伝子改変の導入についての最先端技術になってきている。しかし、それらは、これまでのところ免疫細胞において、外来性コード配列を内在性プロモーターの転写制御下に導入するためには用いられていない。
初代免疫細胞の集団を提供する工程;
該初代免疫細胞のある割合中に、
(i)該免疫細胞集団の治療的可能性を改善する少なくとも1種類の分子をコードするように、選択された内在性遺伝子座に組み込まれる外来性のヌクレオチドまたはポリヌクレオチド配列を含む、少なくとも1種類の核酸;
(ii)該選択された内在性遺伝子座を特異的に標的とする、少なくとも1種類の配列特異的試薬
を導入する工程
を含み、該外来性のヌクレオチドまたはポリヌクレオチド配列は、該内在性遺伝子座中への標的指向遺伝子組込みによって、該遺伝子座に存在する内在性プロモーターの転写制御下に外来性コード配列を形成するように挿入される。
初代免疫細胞の集団を提供する工程;
該初代免疫細胞のある割合中に、
(i)該免疫細胞集団の治療的可能性を改善する少なくとも1種類の分子をコードする外来性コード配列を含む、少なくとも1種類の外来性核酸;
(ii)免疫細胞活性化の間に活性を有している内在性プロモーターの制御下である遺伝子を特異的に標的とする、少なくとも1種類の配列特異的ヌクレアーゼ試薬
を導入する工程
を含み、該コード配列は、該遺伝子の少なくとも1種類の内在性プロモーターの転写制御下に置かれるように、標的指向相同組換えによって初代免疫細胞ゲノム中に導入される。
本発明の1つの局面によると、免疫細胞ゲノム遺伝子座中に組み込まれる外来性配列は、薬物に対する該免疫細胞の耐性を付与する分子をコードする。
本発明の1つの局面によると、免疫細胞ゲノム遺伝子座中に組み込まれる外来性配列は、免疫細胞の残存性、特に、腫瘍環境におけるインビボ残存性を増強する分子をコードする。
T細胞、好ましくは初代T細胞を含む細胞の集団を提供する工程、
該T細胞のある割合中に、
(i)少なくとも1種類のNK細胞阻害物質をコードするように、選択された内在性遺伝子座に組み込まれる外来性ポリヌクレオチド配列を含む、少なくとも1種類の核酸;
(ii)該選択された内在性遺伝子座を特異的に標的とする、少なくとも1種類の配列特異的試薬
を導入する工程
を含み、該外来性ポリヌクレオチド配列が、該内在性遺伝子座中への標的指向遺伝子組込みによって挿入される、前記方法をさらに提供する。
のうちの1つを含むTALリピートを含む任意のエンドヌクレアーゼ配列、ならびにこれらのポリペプチドをコードする任意のポリヌクレオチドおよびベクターに関係する。
1)内在性遺伝子プロモーターの転写制御下に組み込まれている、NK阻害物質をコードする外来性配列を含む、操作されたT細胞。
2)前記内在性遺伝子プロモーターが、表6に列挙される1つの遺伝子座で選択される、項目1のいずれかに記載の操作されたT細胞。
3)NK阻害物質をコードする前記外来性配列が、β2m遺伝子座に組み込まれている、項目1または2のいずれか1つに記載の操作されたT細胞。
4)前記T細胞がキメラ抗原受容体を与えられている、項目1~3のいずれか1つに記載の操作されたT細胞。
5)遺伝子型[TCR]陰性[β2m]陰性[CAR]陽性を有する、項目4に記載の操作されたT細胞。
6)前記CARをコードする外来性配列が、TCR遺伝子座に組み込まれている、項目4または5に記載の操作されたT細胞。
7)前記T細胞が初代細胞である、項目1~6のいずれか1つに記載の操作されたT細胞。
8)がんまたは感染症の処置についてのその使用のための、項目1~7のいずれか1つに記載の操作されたT細胞。
9)少なくとも30%、好ましくは50%、より好ましくは80%の、項目1~8のいずれか1つに記載の操作されたT細胞を含む、治療上有効な免疫細胞の集団。
‐[CAR]陽性[TCR]陰性[β2m]陰性[PD1]陰性
‐[CAR]陽性[TCR]陰性[β2m]陰性[DCK]陰性
‐[CAR]陽性[TCR]陰性[β2m]陰性[CTLA4]陰性
1)少なくとも30%、好ましくは50%、より好ましくは80%の細胞が、ドナー、好ましくは1人の単一ドナーを起源とする、本発明の通りの治療上有効な免疫細胞の集団。
2)50%超の前記免疫細胞が、TCR陰性T細胞である、上記による初代免疫細胞の集団。
3)50%超の前記免疫細胞が、CAR陽性細胞である、上記のような初代免疫細胞の集団。
4)上記のような操作された免疫細胞集団を含む、薬学的組成物。
5)以下の工程を含む、その必要がある患者を処置するための方法:
以前に記載されたような操作された初代免疫細胞の集団を調製する工程;
任意で、該操作された初代免疫細胞を精製または選別する工程;
該操作された初代免疫細胞の集団を、該細胞の該患者中への注入時または注入後に活性化する工程。
6)前記患者が、がんについて処置される、上記のような方法。
7)前記患者が、感染症について処置される、上記のような方法。
1)少なくとも以下の工程を含む、T細胞において発現可能なNK阻害物質をコードする適切な配列を特定するための方法:
TCRおよびβ2mの発現が両方とも抑えられているおよび/または不活性化されているT細胞を提供する工程;
推定のNK阻害物質をコードする候補配列を、該T細胞における内在性プロモーターの制御下の内在性遺伝子座に組み込む工程;
結果として生じた操作されたT細胞を、NK細胞の存在下で培養する工程。
2)少なくとも以下の工程を含む、T細胞において発現可能なNK阻害物質をコードする適切な配列を特定するための方法:
TCR発現が抑えられているかまたは不活性化されているT細胞を提供する工程;
推定のNK阻害物質をコードする候補配列をβ2m遺伝子座に組み込むことによって、該T細胞においてβ2m発現を不活性化する工程であって、該推定のNK阻害物質の発現が、該β2m遺伝子座の内在性プロモーターの転写制御下に置かれる、工程;
結果として生じた操作されたT細胞を、NK細胞の存在下で培養する工程。
3)前記T細胞にキメラ抗原受容体を与える工程
をさらに含む、上記のような方法。
4)前記結果として生じた操作されたT細胞の生存を、前記候補配列を発現しない同じものと比較する工程;
任意で、NK細胞に対してより耐性である操作された細胞を選択する工程
をさらに含む、上記のような方法。
本方法の1つの局面によると、免疫細胞ゲノム遺伝子座中に組み込まれる外来性配列は、免疫細胞の治療活性を増強する分子をコードする。
キメラ抗原受容体(CAR)を発現させることは、腫瘍または感染細胞を処置するために、初代免疫細胞、例えばT細胞およびNK細胞の特異性を指示するまたは改善するための先端技術になってきている。これらの免疫細胞によって発現するCARは、病的細胞の表面の抗原マーカーを特異的に標的とし、これは、該免疫細胞がインビボでこれらの細胞を破壊することをさらに助ける(Sadelain M. et al. "The basic principles of chimeric antigen receptor design" (2013) Cancer Discov. 3(4):388-98)。CARは通常、特異的抗原への結合に応答して免疫細胞を刺激する活性化ドメインを含むように設計されるが(いわゆる正のCAR)、反対の効果を有する阻害性ドメインを含んでもよい(いわゆる負のCAR)(Fedorov, V. D. (2014) "Novel Approaches to Enhance the Specificity and Safety of Engineered T Cells" Cancer Journal 20 (2):160-165)。標的細胞の表面に存在する種々の抗原に応じて細胞免疫特異性を微調整するために、正および負のCARを組み合わせるか、または同時発現させてもよい。
‐アナキンラ(CAS登録番号:143090-92-0)(商品名Kineret)は、インターロイキン1受容体アンタゴニスト(IL1-RA)の組換えバージョンである。アナキンラは、そのアミノ末端での単一メチオニン残基の付加によってネイティブヒトIL-1Raと異なるように、IL1RAのバリアント型である。アナキンラは、天然に存在するIL-1の生物活性を遮断する[Kalliolias, GD. et al. (2008) The future of the IL-1 receptor antagonist anakinra: from rheumatoid arthritis to adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis. Expert Opin Investig Drugs. 17(3):349-59]。
‐リロナセプト(CAS登録番号:501081-76-1)は、IL-1 Trap(商品名ArcalystでRegeneron Pharmaceuticalsによって市販されている)としても公知であり、同様にインターロイキン1阻害物質である。これは、ヒトIgG1の断片結晶化部分(Fc領域)に直列に連結された、ヒトインターロイキン-1受容体構成要素(IL-1R1)およびIL-1受容体アクセサリータンパク質(IL-1RAcP)の細胞外部分のリガンド結合ドメインからなる二量体融合タンパク質であり、IL-1に結合して中和する[McDermott, M.F., (2009) Rilonacept in the treatment of chronic inflammatory disorders. Drugs of Today. 45(6):423-430]。
‐カナキヌマブ(商品名Ilaris、CAS登録番号:914613-48-2)は、インターロイキン-1βを標的としたヒトモノクローナル抗体である。これは、インターロイキン-1αを含む、インターロイキン-1ファミリーの他のメンバーとの交差反応性を有さない[Rondeau J.M. et al. (2015) The molecular mode of action and species specificity of canakinumab, a human monoclonal antibody neutralizing IL-1β. MAbs. 7(6):1151-60]。
‐トシリズマブ(商品名Actemra、CAS登録番号:375823-41-9)は、インターロイキン-6受容体(IL-6R)に対するヒト化モノクローナル抗体である[Venkiteshwaran, A. (2009) Tocilizumab. MAbs. 1(5): 432-438]。
‐シルツキシマブ(商品名Sylvant、CAS登録番号:541502-14-1)は、抗IL-6キメラモノクローナル抗体またはcCLB8であり、インターロイキン-6に結合するキメラ(ヒトおよびマウスのタンパク質から作製された)モノクローナル抗体である[Rhee, F. et al. (2010) Siltuximab, a Novel Anti-Interleukin-6 Monoclonal Antibody for Castleman's Disease. Journal of Clinical Oncology 28 (23):3701-3708]。
‐[CAR]陽性[GP130]陽性
‐[CAR]陽性[GP130]陽性[TCR]陰性
‐[CAR]陽性[TCR]陰性[GP130]陽性[PD1]陰性
‐[CAR]陽性[TCR]陰性[GP130]陽性[β2m]陰性
‐[CAR]陽性[GP130]陽性[CD25]陰性
‐[CAR]陽性[TCR]陰性[GP130]陽性[CD25]陰性
‐[CAR]陽性[sGP130]陽性
‐[CAR]陽性[sGP130]陽性[TCR]陰性
‐[CAR]陽性[TCR]陰性[sGP130]陽性[PD1]陰性
‐[CAR]陽性[TCR]陰性[sGP130]陽性[β2m]陰性
‐[CAR]陽性[sGP130]陽性[CD25]陰性
‐[CAR]陽性[TCR]陰性[IL1RA]陽性[CD25]陰性
‐[CAR]陽性[IL1RA]陽性
‐[CAR]陽性[IL1RA]陽性[TCR]陰性
‐[CAR]陽性[TCR]陰性[IL1RA]陽性[PD1]陰性
‐[CAR]陽性[TCR]陰性[IL1RA]陽性[β2m]陰性
‐[CAR]陽性[IL1RA]陽性[CD25]陰性
‐[CAR]陽性[TCR]陰性[IL18BP]陽性[CD25]陰性
‐[CAR]陽性[TCR]陰性[IL18BP]陽性[PD1]陰性
‐[CAR]陽性[TCR]陰性[IL18BP]陽性[β2m]陰性
‐[CAR]陽性[IL18BP]陽性[CD25]陰性
‐[CAR]陽性[TCR]陰性[IL18BP]陽性[CD25]陰性
本明細書は、内在性プロモーター、特にPD1およびCD25とインフレームでのコード配列の効率的な挿入を行うのに有用である、図に示されるようなドナー鋳型および配列特異的試薬、ならびに、該遺伝子座での該外来性配列の適正な挿入を検出するための手段および配列を提供する。
‐IL-15をコードする配列、例えば、SEQ ID NO:50と同一性を示すもの;
‐好ましくはポリヌクレオチド配列SEQ ID NO:45およびSEQ ID NO:46を含む、PD1遺伝子座に相同な上流および下流(左および右とも呼ばれる)の配列;
‐任意で、IL-15受容体の可溶型(sIL-15R)をコードする配列、例えば、SEQ ID NO:50と同一性を示すもの;
‐任意で、少なくとも1個の2Aペプチド切断部位、例えば、SEQ ID NO:53(F2A)、SEQ ID NO:54(P2A)、および/またはSEQ ID NO:55(T2A)のうちの1つ。
‐IL-12aをコードする配列、例えば、SEQ ID NO:47と同一性を示すもの;
‐好ましくはポリヌクレオチド配列SEQ ID NO:45およびSEQ ID NO:46を含む、PD1遺伝子座に相同な上流および下流(左および右とも呼ばれる)の配列;
‐任意で、IL12bをコードする配列、例えば、SEQ ID NO:48と同一性を示すもの;
‐任意で、少なくとも1個の2Aペプチド切断部位、例えば、SEQ ID NO:53(F2A)、SEQ ID NO:54(P2A)、および/またはSEQ ID NO:55(T2A)のうちの1つ。
‐可溶性GP130、好ましくはFcに融合した可溶性gp130をコードする配列、例えば、SEQ ID NO:62と同一性を示すもの;
‐好ましくはポリヌクレオチド配列SEQ ID NO:45およびSEQ ID NO:46を含む、PD1遺伝子座に相同な上流および下流(左および右とも呼ばれる)の配列;
‐任意で、少なくとも1個の2Aペプチド切断部位、例えば、SEQ ID NO:53(F2A)、SEQ ID NO:54(P2A)、および/またはSEQ ID NO:55(T2A)のうちの1つ。
‐IL-15をコードする配列、例えば、SEQ ID NO:50と同一性を示すもの;
‐好ましくはポリヌクレオチド配列SEQ ID NO:43およびSEQ ID NO:44を含む、CD25遺伝子座に相同な上流および下流(左および右とも呼ばれる)の配列;
‐任意で、IL-15受容体の可溶型(sIL-15R)をコードする配列、例えば、SEQ ID NO:50と同一性を示すもの;
‐任意で、少なくとも1個の2Aペプチド切断部位、例えば、SEQ ID NO:53(F2A)、SEQ ID NO:54(P2A)、および/またはSEQ ID NO:55(T2A)のうちの1つ。
‐IL-12aをコードする配列、例えば、SEQ ID NO:47と同一性を示すもの;
‐好ましくはポリヌクレオチド配列SEQ ID NO:43およびSEQ ID NO:44を含む、CD25遺伝子座に相同な上流および下流(左および右とも呼ばれる)の配列;
‐任意で、IL-12bをコードする配列、例えば、SEQ ID NO:48と同一性を示すもの;
‐任意で、少なくとも1個の2Aペプチド切断部位、例えば、SEQ ID NO:53(F2A)、SEQ ID NO:54(P2A)、および/またはSEQ ID NO:55(T2A)のうちの1つ。
‐可溶性GP130、好ましくはFcに融合した可溶性gp130をコードする配列、例えば、SEQ ID NO:62と同一性を示すもの;
‐好ましくはポリヌクレオチド配列SEQ ID NO:43およびSEQ ID NO:44を含む、CD25遺伝子座に相同な上流および下流(左および右とも呼ばれる)の配列;
‐任意で、少なくとも1個の2Aペプチド切断部位、例えば、SEQ ID NO:53(F2A)、SEQ ID NO:54(P2A)、および/またはSEQ ID NO:55(T2A)のうちの1つ。
‐該外来性核酸配列および標的とされる内在性DNA配列に相同な配列を含むAAVベクターを、該細胞中に形質導入する工程、ならびに
‐挿入の遺伝子座で該内在性配列を切断するために、配列特異的エンドヌクレアーゼ試薬の発現を導入する工程。
本発明は、その主要な局面の1つにおいて、それらの治療的可能性を改善する外来性配列を発現する、免疫細胞の内在性転写活性を利用することである。
‐例として細胞増大を促進するために有用である、dynabeadsなどのCD3/CD28活性化;
‐例として標的に対する免疫細胞機能を活性化するために有用である、例えばCD3ζ経路を通したCAR活性化;
‐例として病気の臓器においてインサイチュで細胞を活性化するために有用である、疾患症状の出現もしくは分子マーカーに連結された転写活性;
‐例として造血細胞がそれらの免疫機能を獲得する時に、分化の所与のレベルの細胞に治療特性を付与するために、もしくは、特定の系列へのタンパク質を発現するために有用である(図1を参照されたい)、細胞分化;または/ならびに
‐細胞の活性およびそれらの増幅を特定の腫瘍状態(低酸素、低糖など)に再度方向づけるため、または、消耗を阻止し、かつ/もしくは活性化を持続させるために有用である、TME(腫瘍微小環境);
‐CAR T細胞活性に関連する有害事象を和らげるために有用である、CRS(サイトカイン放出症候群)。
本態様に関連する内在性遺伝子座の選択を、表7に列挙する。
前に述べられたように、本発明の方法は、免疫細胞活性化時にその転写活性が好ましくは一過性にまたは10日超にわたるかのいずれかで上方制御される内在性プロモーターの制御下で、遺伝子標的指向挿入を行う工程を提供する。
本発明の1つの局面は、より詳細には、腫瘍微小環境(TME)状態において免疫細胞消耗を阻止する方法に関わる。免疫細胞は、多くの場合、腫瘍耐性を助ける腫瘍の微小環境において見出される栄養素枯渇または分子シグナルに応答して消耗する。本方法は、アルギニン、システイン、トリプトファン、および酸素の欠乏、ならびに細胞外アシドーシス(乳酸蓄積)の下で上方制御される内在性プロモーターの制御下に外来性コード配列を組み込むことによって、免疫細胞を操作する工程を含む。
本発明の1つの局面は、より詳細には、造血幹細胞(HSC)中への導入遺伝子の挿入に関わる。
本発明の特定の局面は、外来性コード配列、特にCARまたはその構成要素を発現する造血系免疫細胞、例えばT細胞またはNK細胞の、上記の操作されたHSCによるインビボ産生に関わる。
本発明の1つの特定の焦点は、ある遺伝子座での初代免疫細胞における遺伝子不活性化を、その発現が該操作された細胞の治療的可能性を改善させる、外来性コード配列の該遺伝子座での組込みによって行うことである。本発明に従って挿入することができる関連性のある外来性コード配列の例は、細胞の治療的可能性に対するそれらの正の効果と関連づけて上記で示されている。本明細書の下記には、好ましくは遺伝子標的指向挿入によって標的とされる内在性遺伝子、およびその不活性化と関連する利点が示される。
本発明の好ましい局面によると、挿入される外来性コード配列は、免疫細胞阻害経路、特に文献において「免疫チェックポイント」と呼ばれているものに関与するタンパク質の発現を低減させるまたは阻止する効果を有する(Pardoll, D.M. (2012) The blockade of immune checkpoints in cancer immunotherapy, Nature Reviews Cancer, 12:252-264)。本発明の意味において、「免疫細胞阻害経路」とは、悪性細胞または感染細胞に対するリンパ球の細胞傷害活性の低減をもたらす、免疫細胞における任意の遺伝子発現を意味する。これは、例として、T細胞に対するTregの活性(T細胞活性を穏やかにする)を駆動することが公知である、FOXP3の発現に関与する遺伝子であることができる。
本発明の別の局面によると、挿入される外来性コード配列は、抑制性サイトカインまたは代謝産物またはそれらの受容体、特に、TGFβ(Uniprot:P01137)、TGFbR(Uniprot:P37173)、IL10(Uniprot:P22301)、IL10R(Uniprot: Q13651および/またはQ08334)、A2aR(Uniprot: P29274)、GCN2(Uniprot: P15442)、ならびにPRDM1(Uniprot: O75626)をコードするまたは正に調節する遺伝子の発現を低減させるまたは阻止する効果を有する。
本発明の別の局面によると、挿入される外来性コード配列は、がんまたは感染症のための標準治療の処置において用いられる化合物、例えば、化学療法において一般的に用いられる薬物であるプリンヌクレオチド類似体(PNA)または6-メルカプトプリン(6MP)および6チオグアニン(6TG)に対する免疫細胞の感受性を担う遺伝子の発現を、低減させるまたは阻止する効果を有する。そのような化合物の作用の様式に関与する遺伝子(「薬物感作遺伝子」と呼ばれる)を低減させるかまたは不活性化することは、それらに対する免疫細胞の耐性を改善する。
本発明の別の局面によると、挿入される外来性コード配列は、薬物標的である受容体またはタンパク質の発現を低減させるまたは阻止する効果を有し、細胞を免疫枯渇薬物処置に対して耐性にする。そのような標的は、操作された免疫細胞を、グルココルチコイド、または、多くのがん処置においてCD52陽性免疫細胞を枯渇させるために用いられるアレムツズマブなどの抗体を用いた免疫枯渇処置に対して耐性にする、グルココルチコイド受容体または抗原であることができる。
本発明の別の局面によると、挿入される外来性コード配列は、BCMA、CS1、およびCD38などの表面抗原の発現を低減させるまたは阻止する効果を有することができ、ここで、そのような抗原は、免疫細胞によって発現するCARによって標的とされるものである。
本発明はまた、単離された形態の下でまたは細胞の集団の一部として、以前に記載された方法のうちの1つに従って取得可能である、様々な操作された免疫細胞にも注目する。
以前に記載されたような本発明の方法に従って、操作された初代免疫細胞の集団を調製する工程;
任意で、該操作された初代免疫細胞を精製または選別する工程;
該操作された初代免疫細胞の集団を、該細胞の該患者中への注入時または注入後に活性化する工程。
遺伝子改変の前であろうと後であろうと、本発明による免疫細胞を、たとえそれらが抗原結合機構から独立して活性化または増殖することができるとしても、活性化または増大させることができる。T細胞は、特に、例えば、米国特許第6,352,694号;第6,534,055号;第6,905,680号;第6,692,964号;第5,858,358号;第6,887,466号;第6,905,681号;第7,144,575号;第7,067,318号;第7,172,869号;第7,232,566号;第7,175,843号;第5,883,223号;第6,905,874号;第6,797,514号;第6,867,041号;および米国特許出願公開第20060121005号に記載されているような方法を用いて活性化および増大させることができる。T細胞は、インビトロまたはインビボで増大させることができる。T細胞は、概して、T細胞用の活性化シグナルを創り出すための、T細胞の表面上のCD3 TCR複合体および共刺激分子を刺激する作用物質との接触によって増大させる。例えば、カルシウムイオノフォアA23187、ホルボール12-ミリスタート13-アセタート(PMA)、またはフィトヘマグルチニン(PHA)のような分裂促進性レクチンなどの化学物質を用いて、T細胞用の活性化シグナルを創り出すことができる。
上記の本発明の方法により、操作された初代免疫細胞を、それらが特にその細胞傷害活性に関してその完全な免疫治療的可能性を保つように、約15~30日、好ましくは15~20日の間、および最も好ましくは18~20日の間の限定された時間枠内で作製することが可能になる。
(a)患者の腫瘍生検の表面に存在する特異的抗原マーカーを決定する工程;
(b)該特異的抗原マーカーに向けられたCARを発現する、以前に記載された本発明の方法のうちの1つによって操作された、操作された初代免疫細胞の集団を提供する工程;
(c)操作された初代免疫細胞の該操作された集団を、該患者に投与する工程。
ポリペプチド配列中のアミノ酸残基は、本明細書において1文字表記に従って称され、例えば、Qは、Glnまたはグルタミン残基を意味し、Rは、Argまたはアルギニン残基を意味し、Dは、Aspまたはアスパラギン酸残基を意味する。
序文
配列特異的エンドヌクレアーゼ試薬、例えば、TALEN(登録商標)(Cellectis, 8 rue de la Croix Jarry, 75013 PARIS)は、所望の遺伝子座でのゲノムにおける二本鎖切断(DSB)の部位特異的導入を可能にする。細胞酵素によるDSBの修復は、主に、2つの経路:非相同末端結合(NHEJ)および相同性指向修復(HDR)を通して起こる。HDRは、DNAの相同な片(鋳型DNA)を用いて、組換えによりDSBを修復し、鋳型DNAに含まれる任意の遺伝子配列を導入するために用いられ得る。その中で示されるように、前記鋳型DNAは、部位特異的DSBを導入するために、操作されたヌクレアーゼ、例えばTALEN(登録商標)と共に組換えアデノ随伴ウイルス(rAAV)によって送達され得る。
1.1. 内在性PD1遺伝子コード配列のノックアウトを伴う、上方制御される遺伝子座におけるアポトーシスCARの挿入
TALEN標的部位の位置を、標的とされる内在性PDCD1遺伝子(PD1と呼ばれるプログラム細胞死タンパク質1 - Uniprot # Q15116)に位置するように設計している。TALEN標的の1000 bp上流および下流を包含する配列を、SEQ ID NO.1およびSEQ ID NO.2に示す。TALEN(SEQ ID: SEQ ID NO.3およびNO.4)の標的配列を、SEQ ID NO.5に示す。組込みマトリックスを、TALEN部位の内在性遺伝子上流に相同な配列(300 bp)(SEQ ID NO.1)、その後の2A調節エレメント(SEQ ID NO.6)、その後の開始コドンを伴わないアポトーシス誘導CARをコードする配列(SEQ ID NO.7)、その後の終止コドン(TAG)、その後のポリアデニル化配列(SEQ ID NO.8)、その後のTALEN部位の内在性遺伝子下流に相同な配列(1000 bp)(SEQ ID NO.2)から構成されるように設計する。挿入マトリックスを、続いて、プロモーターのないrAAVベクター中にクローニングして、AAV6を産生するために用いる。
TALEN標的部位の位置を、標的とされる内在性PDCD1遺伝子(プログラム細胞死タンパク質1、PD1)に位置するように設計する。TALEN標的の1000 bp上流および下流を包含する配列を、SEQ ID NO.1およびSEQ ID NO.2に示す。TALEN(SEQ ID: SEQ ID NO.3およびNO.4)の標的配列を、SEQ ID NO.5に示す。組込みマトリックスを、TALEN部位の内在性遺伝子上流に相同な配列(300 bp)(SEQ ID NO.1)、その後の2A調節エレメント(SEQ ID NO.6)、その後の操作された一本鎖のヒトIL-12 p35(SEQ ID NO.9)およびp40(SEQ ID NO.10)サブユニット融合タンパク質をコードする配列、その後の終止コドン(TAG)、その後のポリアデニル化配列(SEQ ID NO.8)、その後のTALEN部位の内在性遺伝子下流に相同な配列(1000 bp)(SEQ ID NO.2)から構成されるように設計する。挿入マトリックスを、続いて、プロモーターのないrAAVベクター中にクローニングして、AAV6を産生するために用いる。
TALEN標的部位の位置を、標的とされる内在性LCK遺伝子(LCK、LCKプロトオンコジーン、Srcファミリーチロシンキナーゼ[ホモ・サピエンス(ヒト)])の開始コドンのできるだけ近くに位置するように設計する。開始コドンの1000 bp上流および下流を包含する配列を、SEQ ID NO.11およびSEQ ID NO.12に示す。組込みマトリックスを、開始コドンの内在性遺伝子上流に相同な配列(1000 bp)、その後の開始コドンを含有するアポトーシス誘導CARをコードする配列(SEQ ID NO.13)、その後の2A調節エレメント(SEQ ID NO.8)、その後の開始コドンの内在性遺伝子下流に相同な配列(1000bp)(SEQ ID NO.12)から構成されるように設計する。挿入マトリックスを、続いて、プロモーターのないrAAVベクター中にクローニングして、AAV6を産生するために用いる。
TALEN標的部位の位置を、標的とされる内在性LCK遺伝子(LCK、LCKプロトオンコジーン、Srcファミリーチロシンキナーゼ[ホモ・サピエンス(ヒト)])の終止コドンのできるだけ近くに位置するように設計する。終止コドンの1000 bp上流および下流を包含する配列を、SEQ ID NO.14およびSEQ ID NO.15に示す。組込みマトリックスを、終止コドンの内在性遺伝子上流に相同な配列(1000 bp)、その後の2A調節エレメント(SEQ ID NO.8)、その後の開始コドンを有さないアポトーシス誘導CARをコードする配列(SEQ ID NO.7)、その後の終止コドン(TAG)、その後の終止コドンの内在性遺伝子下流に相同な配列(1000 bp)(SEQ ID NO.15)から構成されるように設計する。挿入マトリックスを、続いて、プロモーターのないrAAVベクター中にクローニングして、AAV6を産生するために用いる。
TALEN(登録商標) mRNAを、mMessage mMachine T7 Ultraキット(Thermo Fisher Scientific, Grand Island, NY)を用いて、各TALENがT7プロモーターの下流にクローニングされるように合成し、RNeasyカラム(Qiagen, Valencia, CA)を用いて精製して、「cytoporation medium T」(Harvard Apparatus, Holliston, MA)において溶出する。ヒトT細胞を、ALLCELLS(Alameda, CA)によって提供される末梢全血から、20 ng/mlヒトIL-2(Miltenyi Biotech, San Diego, CA)、5%ヒトAB血清(Gemini Bio-Products, West San Francisco, CA)、および1:1のビーズ:細胞比のDynabeads Human T-activator CD3/CD28(Thermo Fisher Scientific, Grand Island, NY)を補給したX-Vivo-15培地(Lonza, Basel, Switzerland)において収集し、活性化する。ビーズを3日後に取り除き、5×106細胞に2種類の妥当なTALEN(登録商標)の各々の10μg mRNAを、Cytopulse(BTX Harvard Apparatus, Holliston, MA)を用いて、0.4 cm間隙のキュベット中で200μlの「cytoporation medium T」(BTX Harvard Apparatus, Holliston, Massachusetts)の最終体積において、3,000 V/cmでの2回の0.1 mSパルス、およびその後の325 V/cmでの4回の0.2 mSパルスを印加することによってエレクトロポレーションする。細胞を直ちに、 20 ng/mL IL-2を含むX-Vivo-15培地に希釈し、37℃、5% CO2でインキュベートする。2時間後、細胞を、1細胞あたり3×105ウイルスゲノム(vg)のAAV6粒子とインキュベートする(37℃、16時間)。細胞を、それぞれの挿入された遺伝子配列の発現についてフローサイトメトリーによって検討するまで、5%ヒトAB血清および20 ng/mL IL-2を補給したX-Vivo-15培地において継代し、維持する。
材料
X-vivo-15をLonza(カタログ番号BE04-418Q)から、IL-2をMiltenyi Biotech(カタログ番号130-097-748)から、ヒト血清ABをSeralab(カタログ番号GEM-100-318)から、human T activator CD3/CD28をLife Technology(カタログ番号11132D)から、QBEND10-APCをR&D Systems(カタログ番号FAB7227A)から、vioblue標識抗CD3、PE標識抗LNGFR、APC標識抗CD25、およびPE標識抗PD1をMiltenyi(それぞれ、カタログ番号130-094-363、130-112-790、130-109-021、および130-104-892)から、 48ウェル処理プレート(CytoOne, カタログ番号CC7682-7548)を、ヒトIL-15 Quantikine ELISAキットをR&D systems(カタログ番号S1500)から、ONE-GloをPromega(カタログ番号E6110)から入手した。様々なマトリックスを含有するAAV6バッチをVirovekから入手し、PBMC細胞をAllcells(カタログ番号PB004F)から入手し、Raji-ルシフェラーゼ細胞を、ATCC(カタログ番号CCL-86)由来のRaji細胞のホタルルシフェラーゼをコードするレンチウイルス粒子の形質導入後に得た。
2.1-トランスフェクション-形質導入
TRACおよびPD1またはCD25遺伝子座での二重標的指向組込みを、以下のように行った。PBMC細胞を、X-vivo-15完全培地(X-vivo-15、5%AB血清、20 ng/mL IL-2)において最初に融解し、洗浄し、再懸濁して培養した。1日後に、細胞を、Dynabeads human T activator CD3/CD28(25μLのビーズ/1E6 CD3陽性細胞)によって活性化し、1E6細胞/mLの密度で3日間、X-vivo完全培地において37℃で、5% CO2の存在下で培養した。細胞を、次いで、新鮮な完全培地において分割し、以下の手順に従って次の日に形質導入/トランスフェクトした。形質導入-トランスフェクションの日に、細胞を最初に、磁気分離(EasySep)によって脱ビーズ化(de-beaded)し、Cytoporation buffer T(BTX Harvard Apparatus, Holliston, Massachusetts)において2回洗浄して、同じ溶液に28E6細胞/mLの最終濃度で再懸濁した。細胞懸濁液を、200μlの最終体積において、TRAC TALEN(登録商標)アーム(SEQ ID NO:16および17)をコードする5μg mRNAと、CD25またはPD1 TALEN(登録商標)のいずれかのアーム(それぞれSEQ ID NO:18および19ならびにSEQ ID NO:20および21)をコードする15μgのmRNAの存在下または非存在下で混合した。TALEN(登録商標)は、TALEとFok-1との融合に起因するTALEヌクレアーゼの標準形式である。トランスフェクションは、Pulse Agile技術を用いて、0.4 cm間隙のキュベット中で200μlのCytoporation buffer T(BTX Harvard Apparatus, Holliston, Massachusetts)の最終体積において、3,000 V/cmでの2回の0.1 mSパルス、およびその後の325 V/cmでの4回の0.2 mSパルスを印加することによって行った。エレクトロポレーションした細胞を、次いで直ちに、1 mLのあらかじめ温めたX-vivo-15無血清培地を含有する12ウェルプレートに移し、37℃で15分間インキュベートした。細胞を、次いで、48ウェルレギュラー処理プレート中で、ドナーマトリックスを含むAAV6粒子(MOI=3E5 vg/細胞)の存在下で、250μLの同じ培地において8E6 細胞/mLに濃縮した。30℃での2時間の培養後に、 250 μLの、10% AB血清および40 ng/ml IL-2を補給したXvivo-15培地を細胞懸濁液に添加し、混合物を24時間、同じ培養条件でインキュベートした。1日後に、細胞を、完全X-vivo-15培地において1E6細胞/mLで播種し、37℃で、5% CO2の存在下で培養した。
操作されたT細胞を、以前に記載されたトランスフェクション-形質導入プロセスから回収し、100μL最終体積の完全X-vivo-15培地において単独で、またはRaji細胞(E:T=1:1)もしくはDynabeads(12.5μL/1E6細胞)の存在下で、1E6細胞/mLで播種した。細胞を、48時間培養し、その後回収し、標識して、フローサイトメトリーによって解析した。細胞を、2種類の独立した抗体のセットで標識した。第1の抗体のセットは、ΔLNGFR、CAR、およびCD3細胞の存在の検出を目標にして、QBEND10-APC(1/10希釈)、vioblue標識抗CD3(1/25希釈)、およびPE標識抗ΔLNGFR(1/25希釈)からなった。第2の抗体のセットは、内在性CD25およびPD1の発現の検出を目標にして、APC標識抗CD25(1/25希釈)およびvioblue標識抗PD1(1/25希釈)からなった。
操作されたCAR T細胞の抗腫瘍活性を評価するために、連続死滅アッセイを行った。このアッセイの原理は、一定量の腫瘍細胞の毎日の添加によって、CAR T細胞抗腫瘍活性に毎日挑戦するものである。腫瘍細胞増殖、制御、および再発を、腫瘍細胞株に安定に組み込まれたルシフェラーゼマーカーのおかげで、発光読み取りを介してモニタリングすることができた。
本実施例は、IL-15/可溶性IL-15受容体αヘテロ二量体(IL15/sIL15rα)発現カセットを、PD1およびCD25遺伝子を調節する内在性T細胞プロモーターの制御下に組み込むことによって、CAR T細胞療法の治療転帰を改善する方法を記載する。遺伝子は両方とも、CAR T細胞による腫瘍係合時に上方制御されることが公知であるため、それらを乗っ取って腫瘍の近傍においてのみIL-IL15/sIL15rαを再発現させることができる。本方法は、活性化誘導性T細胞死(AICD)を低減させる、T細胞生存を促進する、T細胞抗腫瘍活性を増強する、およびT細胞アネルギーを逆転させるその能力を維持しながら、IL15/sIL15rα全身性分泌の潜在的な副作用を低減させることを目標にする。
本実施例は、CAR T細胞療法の治療転帰を、インビボでのその残存性を延長させることによって改善する方法を記載する。これは、CARをTRAC遺伝子座に、およびNK阻害物質をB2M遺伝子座に送達するAAV6修復ベクターの存在下での、B2MおよびTCRの同時TALEN(登録商標)媒介性ノックアウトにある。本方法は、CAR T細胞が、非特異的かつTCR媒介性の様式で宿主組織を攻撃すること(移植片対宿主攻撃)、ならびにCAR T細胞の宿主T細胞およびNK細胞媒介性枯渇を転用することを阻止する。
‐B2m遺伝子座に挿入され得る、VMAPRTLFLペプチドを含むHLAE三量体マトリックス(SEQ ID NO.68)(SEQ ID NO.69)、
‐B2m遺伝子座に挿入され得る、VMAPRTLILペプチドを含むHLAE三量体マトリックス(SEQ ID NO.70)(SEQ ID NO.71)、
‐B2m遺伝子座に挿入され得る、UL18三量体マトリックス_Actineペプチド(SEQ ID NO.72)(SEQ ID NO.73)、
‐B2m遺伝子座に挿入され得る、UL18三量体マトリックス_HLACwペプチド(SEQ ID NO.74)(SEQ ID NO.75)、
‐B2m遺伝子座に挿入され得る、UL18三量体マトリックス_HLAG(SEQ ID NO.76)(SEQ ID NO.77)。
HLAG1(SEQ ID NO.84)
HLAG2(SEQ ID NO.85)
HLAG3(SEQ ID NO.86)
HLAG4(SEQ ID NO.87)
HLAG5(SEQ ID NO.88)
HLAG6(SEQ ID NO.89)
HLAG7(SEQ ID NO.90)
ペプチド1 VMAPRTLIL
ペプチド2 VMAPRTLLL
ペプチド3 VMAPRTLVL
ペプチド4 AMAPRTLIL
ペプチド5 VMAPRSLIL
ペプチド6 VMAPRSLLL
ペプチド7 VMAPRTLFL
ペプチド8 VMAPRILIL
ペプチド9 YLLPRRGPRL
ペプチド10 ALPHAILRL
SEQUENCE LISTING
<110> Cellectis
<120> TARGETED GENE INTEGRATION OF NK INHIBITORS GENES FOR IMPROVED IMMUNE CELLS THERAPY
<150> EP PCT/EP2017/076798
<151> 2017-10-19
<150> EP PCT/EP2018/053343
<151> 2018-02-09
<160> 90
<170> PatentIn version 3.5
<210> 1
<211> 1000
<212> DNA
<213> artificial sequence
<220>
<223> PD1 left homology
<400> 1
ccaagccctg accctggcag gcatatgttt caggaggtcc ttgtcttggg agcccagggt 60
cgggggcccc gtgtctgtcc acatccgagt caatggccca tctcgtctct gaagcatctt 120
tgctgtgagc tctagtcccc actgtcttgc tggaaaatgt ggaggcccca ctgcccactg 180
cccagggcag caatgcccat accacgtggt cccagctccg agcttgtcct gaaaaggggg 240
caaagactgg accctgagcc tgccaagggg ccacactcct cccagggctg gggtctccat 300
gggcagcccc ccacccaccc agaccagtta cactcccctg tgccagagca gtgcagacag 360
gaccaggcca ggatgcccaa gggtcagggg ctggggatgg gtagccccca aacagccctt 420
tctgggggaa ctggcctcaa cggggaaggg ggtgaaggct cttagtagga aatcagggag 480
acccaagtca gagccaggtg ctgtgcagaa gctgcagcct cacgtagaag gaagaggctc 540
tgcagtggag gccagtgccc atccccgggt ggcagaggcc ccagcagaga cttctcaatg 600
acattccagc tggggtggcc cttccagagc ccttgctgcc cgagggatgt gagcaggtgg 660
ccggggaggc tttgtggggc cacccagccc cttcctcacc tctctccatc tctcagactc 720
cccagacagg ccctggaacc cccccacctt ctccccagcc ctgctcgtgg tgaccgaagg 780
ggacaacgcc accttcacct gcagcttctc caacacatcg gagagcttcg tgctaaactg 840
gtaccgcatg agccccagca accagacgga caagctggcc gccttccccg aggaccgcag 900
ccagcccggc caggactgcc gcttccgtgt cacacaactg cccaacgggc gtgacttcca 960
catgagcgtg gtcagggccc ggcgcaatga cagcggcacc 1000
<210> 2
<211> 1000
<212> DNA
<213> artificial sequence
<220>
<223> PD1 right homology
<400> 2
gcctgcgggc agagctcagg gtgacaggtg cggcctcgga ggccccgggg caggggtgag 60
ctgagccggt cctggggtgg gtgtcccctc ctgcacagga tcaggagctc cagggtcgta 120
gggcagggac cccccagctc cagtccaggg ctctgtcctg cacctgggga atggtgaccg 180
gcatctctgt cctctagctc tggaagcacc ccagcccctc tagtctgccc tcacccctga 240
ccctgaccct ccaccctgac cccgtcctaa cccctgacct ttgtgccctt ccagagagaa 300
gggcagaagt gcccacagcc caccccagcc cctcacccag gccagccggc cagttccaaa 360
ccctggtggt tggtgtcgtg ggcggcctgc tgggcagcct ggtgctgcta gtctgggtcc 420
tggccgtcat ctgctcccgg gccgcacgag gtaacgtcat cccagcccct cggcctgccc 480
tgccctaacc ctgctggcgg ccctcactcc cgcctcccct tcctccaccc ttccctcacc 540
ccaccccacc tccccccatc tccccgccag gctaagtccc tgatgaaggc ccctggacta 600
agacccccca cctaggagca cggctcaggg tcggcctggt gaccccaagt gtgtttctct 660
gcagggacaa taggagccag gcgcaccggc cagcccctgg tgagtctcac tcttttcctg 720
catgatccac tgtgccttcc ttcctgggtg ggcagaggtg gaaggacagg ctgggaccac 780
acggcctgca ggactcacat tctattatag ccaggacccc acctccccag cccccaggca 840
gcaacctcaa tccctaaagc catgatctgg ggccccagcc cacctgcggt ctccgggggt 900
gcccggccca tgtgtgtgcc tgcctgcggt ctccaggggt gcctggccca cgcgtgtgcc 960
cgcctgcggt ctctgggggt gcccggccca catatgtgcc 1000
<210> 3
<211> 2781
<212> DNA
<213> artificial sequence
<220>
<223> PD1_T3C-L2
<400> 3
atgggcgatc ctaaaaagaa acgtaaggtc atcgatatcg ccgatctacg cacgctcggc 60
tacagccagc agcaacagga gaagatcaaa ccgaaggttc gttcgacagt ggcgcagcac 120
cacgaggcac tggtcggcca cgggtttaca cacgcgcaca tcgttgcgtt aagccaacac 180
ccggcagcgt tagggaccgt cgctgtcaag tatcaggaca tgatcgcagc gttgccagag 240
gcgacacacg aagcgatcgt tggcgtcggc aaacagtggt ccggcgcacg cgctctggag 300
gccttgctca cggtggcggg agagttgaga ggtccaccgt tacagttgga cacaggccaa 360
cttctcaaga ttgcaaaacg tggcggcgtg accgcagtgg aggcagtgca tgcatggcgc 420
aatgcactga cgggtgcccc gctcaacttg acccccgagc aagtggtggc tatcgcttcc 480
aagctggggg gaaagcaggc cctggagacc gtccaggccc ttctcccagt gctttgccag 540
gctcacggac tgacccctga acaggtggtg gcaattgcct cacacgacgg gggcaagcag 600
gcactggaga ctgtccagcg gctgctgcct gtcctctgcc aggcccacgg actcactcct 660
gagcaggtcg tggccattgc cagccacgat gggggcaaac aggctctgga gaccgtgcag 720
cgcctcctcc cagtgctgtg ccaggctcat gggctgaccc cacagcaggt cgtcgccatt 780
gccagtaacg gcggggggaa gcaggccctc gaaacagtgc agaggctgct gcccgtcttg 840
tgccaagcac acggcctgac acccgagcag gtggtggcca tcgcctctca tgacggcggc 900
aagcaggccc ttgagacagt gcagagactg ttgcccgtgt tgtgtcaggc ccacgggttg 960
acaccccagc aggtggtcgc catcgccagc aatggcgggg gaaagcaggc ccttgagacc 1020
gtgcagcggt tgcttccagt gttgtgccag gcacacggac tgacccctca acaggtggtc 1080
gcaatcgcca gctacaaggg cggaaagcag gctctggaga cagtgcagcg cctcctgccc 1140
gtgctgtgtc aggctcacgg actgacacca cagcaggtgg tcgccatcgc cagtaacggg 1200
ggcggcaagc aggctttgga gaccgtccag agactcctcc ccgtcctttg ccaggcccac 1260
gggttgacac ctcagcaggt cgtcgccatt gcctccaaca acgggggcaa gcaggccctc 1320
gaaactgtgc agaggctgct gcctgtgctg tgccaggctc atgggctgac accccagcag 1380
gtggtggcca ttgcctctaa caacggcggc aaacaggcac tggagaccgt gcaaaggctg 1440
ctgcccgtcc tctgccaagc ccacgggctc actccacagc aggtcgtggc catcgcctca 1500
aacaatggcg ggaagcaggc cctggagact gtgcaaaggc tgctccctgt gctctgccag 1560
gcacacggac tgacccctca gcaggtggtg gcaatcgctt ccaacaacgg gggaaagcag 1620
gccctcgaaa ccgtgcagcg cctcctccca gtgctgtgcc aggcacatgg cctcacaccc 1680
gagcaagtgg tggctatcgc cagccacgac ggagggaagc aggctctgga gaccgtgcag 1740
aggctgctgc ctgtcctgtg ccaggcccac gggcttactc cagagcaggt cgtcgccatc 1800
gccagtcatg atggggggaa gcaggccctt gagacagtcc agcggctgct gccagtcctt 1860
tgccaggctc acggcttgac tcccgagcag gtcgtggcca ttgcctcaaa cattgggggc 1920
aaacaggccc tggagacagt gcaggccctg ctgcccgtgt tgtgtcaggc ccacggcttg 1980
acaccccagc aggtggtcgc cattgcctct aatggcggcg ggagacccgc cttggagagc 2040
attgttgccc agttatctcg ccctgatccg gcgttggccg cgttgaccaa cgaccacctc 2100
gtcgccttgg cctgcctcgg cgggcgtcct gcgctggatg cagtgaaaaa gggattgggg 2160
gatcctatca gccgttccca gctggtgaag tccgagctgg aggagaagaa atccgagttg 2220
aggcacaagc tgaagtacgt gccccacgag tacatcgagc tgatcgagat cgcccggaac 2280
agcacccagg accgtatcct ggagatgaag gtgatggagt tcttcatgaa ggtgtacggc 2340
tacaggggca agcacctggg cggctccagg aagcccgacg gcgccatcta caccgtgggc 2400
tcccccatcg actacggcgt gatcgtggac accaaggcct actccggcgg ctacaacctg 2460
cccatcggcc aggccgacga aatgcagagg tacgtggagg agaaccagac caggaacaag 2520
cacatcaacc ccaacgagtg gtggaaggtg tacccctcca gcgtgaccga gttcaagttc 2580
ctgttcgtgt ccggccactt caagggcaac tacaaggccc agctgaccag gctgaaccac 2640
atcaccaact gcaacggcgc cgtgctgtcc gtggaggagc tcctgatcgg cggcgagatg 2700
atcaaggccg gcaccctgac cctggaggag gtgaggagga agttcaacaa cggcgagatc 2760
aacttcgcgg ccgactgata a 2781
<210> 4
<211> 2778
<212> DNA
<213> artificial sequence
<220>
<223> PD1T3R
<400> 4
atgggcgatc ctaaaaagaa acgtaaggtc atcgatatcg ccgatctacg cacgctcggc 60
tacagccagc agcaacagga gaagatcaaa ccgaaggttc gttcgacagt ggcgcagcac 120
cacgaggcac tggtcggcca cgggtttaca cacgcgcaca tcgttgcgtt aagccaacac 180
ccggcagcgt tagggaccgt cgctgtcaag tatcaggaca tgatcgcagc gttgccagag 240
gcgacacacg aagcgatcgt tggcgtcggc aaacagtggt ccggcgcacg cgctctggag 300
gccttgctca cggtggcggg agagttgaga ggtccaccgt tacagttgga cacaggccaa 360
cttctcaaga ttgcaaaacg tggcggcgtg accgcagtgg aggcagtgca tgcatggcgc 420
aatgcactga cgggtgcccc gctcaacttg acccccgagc aagtcgtcgc aatcgccagc 480
catgatggag ggaagcaagc cctcgaaacc gtgcagcggt tgcttcctgt gctctgccag 540
gcccacggcc ttacccctca gcaggtggtg gccatcgcaa gtaacggagg aggaaagcaa 600
gccttggaga cagtgcagcg cctgttgccc gtgctgtgcc aggcacacgg cctcacacca 660
gagcaggtcg tggccattgc ctcccatgac ggggggaaac aggctctgga gaccgtccag 720
aggctgctgc ccgtcctctg tcaagctcac ggcctgactc cccaacaagt ggtcgccatc 780
gcctctaatg gcggcgggaa gcaggcactg gaaacagtgc agagactgct ccctgtgctt 840
tgccaagctc atgggttgac cccccaacag gtcgtcgcta ttgcctcaaa cggggggggc 900
aagcaggccc ttgagactgt gcagaggctg ttgccagtgc tgtgtcaggc tcacgggctc 960
actccacaac aggtggtcgc aattgccagc aacggcggcg gaaagcaagc tcttgaaacc 1020
gtgcaacgcc tcctgcccgt gctctgtcag gctcatggcc tgacaccaca acaagtcgtg 1080
gccatcgcca gtaataatgg cgggaaacag gctcttgaga ccgtccagag gctgctccca 1140
gtgctctgcc aggcacacgg gctgaccccc gagcaggtgg tggctatcgc cagcaatatt 1200
gggggcaagc aggccctgga aacagtccag gccctgctgc cagtgctttg ccaggctcac 1260
gggctcactc cccagcaggt cgtggcaatc gcctccaacg gcggagggaa gcaggctctg 1320
gagaccgtgc agagactgct gcccgtcttg tgccaggccc acggactcac acctgaacag 1380
gtcgtcgcca ttgcctctca cgatgggggc aaacaagccc tggagacagt gcagcggctg 1440
ttgcctgtgt tgtgccaagc ccacggcttg actcctcaac aagtggtcgc catcgcctca 1500
aatggcggcg gaaaacaagc tctggagaca gtgcagaggt tgctgcccgt cctctgccaa 1560
gcccacggcc tgactcccca acaggtcgtc gccattgcca gcaacaacgg aggaaagcag 1620
gctctcgaaa ctgtgcagcg gctgcttcct gtgctgtgtc aggctcatgg gctgaccccc 1680
gagcaagtgg tggctattgc ctctaatgga ggcaagcaag cccttgagac agtccagagg 1740
ctgttgccag tgctgtgcca ggcccacggg ctcacacccc agcaggtggt cgccatcgcc 1800
agtaacaacg ggggcaaaca ggcattggaa accgtccagc gcctgcttcc agtgctctgc 1860
caggcacacg gactgacacc cgaacaggtg gtggccattg catcccatga tgggggcaag 1920
caggccctgg agaccgtgca gagactcctg ccagtgttgt gccaagctca cggcctcacc 1980
cctcagcaag tcgtggccat cgcctcaaac ggggggggcc ggcctgcact ggagagcatt 2040
gttgcccagt tatctcgccc tgatccggcg ttggccgcgt tgaccaacga ccacctcgtc 2100
gccttggcct gcctcggcgg gcgtcctgcg ctggatgcag tgaaaaaggg attgggggat 2160
cctatcagcc gttcccagct ggtgaagtcc gagctggagg agaagaaatc cgagttgagg 2220
cacaagctga agtacgtgcc ccacgagtac atcgagctga tcgagatcgc ccggaacagc 2280
acccaggacc gtatcctgga gatgaaggtg atggagttct tcatgaaggt gtacggctac 2340
aggggcaagc acctgggcgg ctccaggaag cccgacggcg ccatctacac cgtgggctcc 2400
cccatcgact acggcgtgat cgtggacacc aaggcctact ccggcggcta caacctgccc 2460
atcggccagg ccgacgaaat gcagaggtac gtggaggaga accagaccag gaacaagcac 2520
atcaacccca acgagtggtg gaaggtgtac ccctccagcg tgaccgagtt caagttcctg 2580
ttcgtgtccg gccacttcaa gggcaactac aaggcccagc tgaccaggct gaaccacatc 2640
accaactgca acggcgccgt gctgtccgtg gaggagctcc tgatcggcgg cgagatgatc 2700
aaggccggca ccctgaccct ggaggaggtg aggaggaagt tcaacaacgg cgagatcaac 2760
ttcgcggccg actgataa 2778
<210> 5
<211> 49
<212> DNA
<213> artificial sequence
<220>
<223> PD1-T3
<400> 5
tacctctgtg gggccatctc cctggccccc aaggcgcaga tcaaagaga 49
<210> 6
<211> 60
<212> DNA
<213> artificial sequence
<220>
<223> 2A-element
<400> 6
tccggtgagg gcagaggaag tcttctaaca tgcggtgacg tggaggagaa tccgggcccc 60
<210> 7
<211> 1989
<212> DNA
<213> artificial sequence
<220>
<223> apoptosis CAR
<400> 7
gctttgcctg tcactgcctt gctgcttcca cttgctctgt tgttgcacgc cgcaagaccc 60
gaggtcaagc tccaggaaag cggaccaggg ctggtggccc ctagtcagtc attgagcgtc 120
acttgcaccg tcagcggcgt gtctctgccc gattacggcg tgagctggat cagacagccc 180
ccaaggaagg gactggagtg gctgggcgtc atctggggga gcgagactac ctactacaac 240
agcgccctga agagcaggct gaccatcatt aaggacaact ccaagtccca ggtctttctg 300
aaaatgaaca gcctgcagac tgatgacact gccatctact actgcgccaa gcattactac 360
tacgggggca gctacgctat ggactactgg gggcagggga cctctgtcac agtgtcaagt 420
ggcggaggag gcagtggcgg agggggaagt gggggcggcg gcagcgacat ccagatgacc 480
cagacaacat ccagcctctc cgcctctctg ggcgacagag tgacaatcag ctgccgggcc 540
agtcaggaca tcagcaagta tctcaattgg taccagcaga aaccagacgg gacagtgaaa 600
ttgctgatct accacacatc caggctgcac tcaggagtcc ccagcaggtt ttccggctcc 660
ggctccggga cagattacag tctgaccatt tccaacctgg agcaggagga tattgccaca 720
tacttttgcc agcaaggcaa cactctgccc tataccttcg gcggaggcac aaaactggag 780
attactcggt cggatcccga gcccaaatct cctgacaaaa ctcacacatg cccaccgtgc 840
ccagcacctc ccgtggccgg cccgtcagtg ttcctcttcc ccccaaaacc caaggacacc 900
ctcatgatcg cccggacccc tgaggtcaca tgcgtggtgg tggacgtgag ccacgaggac 960
cctgaggtca agttcaactg gtacgtggac ggcgtggagg tgcataatgc caagacaaag 1020
ccgcgggagg agcagtacaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac 1080
caggactggc tgaatggcaa ggagtacaag tgcaaggtgt ccaacaaagc cctcccagcc 1140
cccatcgaga aaaccatctc caaagccaaa gggcagcccc gagaaccaca ggtgtacacc 1200
ctgcccccat cccgggatga gctgaccaag aaccaggtca gcctgacctg cctggtcaaa 1260
ggcttctatc ccagcgacat cgccgtggag tgggagagca atgggcaacc ggagaacaac 1320
tacaagacca cgcctcccgt gctggactcc gacggctcct tcttcctcta cagcaagctc 1380
accgtggaca agagcaggtg gcagcagggg aacgtgttct catgctccgt gatgcatgag 1440
gccctgcaca atcactatac ccagaaatct ctgagtctga gcccaggcaa gaaggatatt 1500
ttggggtggc tttgccttct tcttttgcca attccactaa ttgtttgggt gaagagaaag 1560
gaagtacaga aaacatgcag aaagcacaga aaggaaaacc aaggttctca tgaatctcca 1620
accttaaatc ctgaaacagt ggcaataaat ttatctgatg ttgacttgag taaatatatc 1680
accactattg ctggagtcat gacactaagt caagttaaag gctttgttcg aaagaatggt 1740
gtcaatgaag ccaaaataga tgagatcaag aatgacaatg tccaagacac agcagaacag 1800
aaagttcaac tgcttcgtaa ttggcatcaa cttcatggaa agaaagaagc gtatgacaca 1860
ttgattgcag atctcaaaaa agccaatctt tgtactcttg cagagaaaat tcagactatc 1920
atcctcaagg acattactag tgactcagaa aattcaaact tcagaaatga aatccagagc 1980
ttggtcgaa 1989
<210> 8
<211> 276
<212> DNA
<213> artificial sequence
<220>
<223> BGH polyA
<400> 8
tctagagggc ccgtttaaac ccgctgatca gcctcgactg tgccttctag ttgccagcca 60
tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc 120
ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca ttctattctg 180
gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag caggcatgct 240
ggggatgcgg tgggctctat gactagtggc gaattc 276
<210> 9
<211> 1000
<212> DNA
<213> artificial sequence
<220>
<223> Lck left homology
<400> 9
gggatagggg gtgcctctgt gtgtgtgtgt gagagtgtgt gtgtgtaggg tgtgtatatg 60
tatagggtgt gtgtgagtgt gtgtgtgtga gagagtgtgt gtgtggcaga atagactgcg 120
gaggtggatt tcatcttgat atgaaaggtc tggaatgcat ggtacattaa actttgagga 180
cagcgctttc caagcactct gaggagcagc cctagagaag gaggagctgc agggactccg 240
ggggcttcaa agtgagggcc ccactctgct tcaggcaaaa caggcacaca tttatcactt 300
tatctatgga gttctgcttg atttcatcag acaaaaaatt tccactgcta aaacaggcaa 360
ataaacaaaa aaaaagttat ggccaacaga gtcactggag ggttttctgc tggggagaag 420
caagcccgtg tttgaaggaa ccctgtgaga tgactgtggg ctgtgtgagg ggaacagcgg 480
gggcttgatg gtggacttcg ggagcagaag cctctttctc agcctcctca gctagacagg 540
ggaattataa taggaggtgt ggcgtgcaca cctctccagt aggggagggt ctgataagtc 600
aggtctctcc caggcttggg aaagtgtgtg tcatctctag gaggtggtcc tcccaacaca 660
gggtactggc agagggagag ggagggggca gaggcaggaa gtgggtaact agactaacaa 720
aggtgcctgt ggcggtttgc ccatcccagg tgggagggtg gggctagggc tcaggggccg 780
tgtgtgaatt tacttgtagc ctgagggctc agagggagca ccggtttgga gctgggaccc 840
cctattttag cttttctgtg gctggtgaat ggggatccca ggatctcaca atctcaggta 900
cttttggaac tttccagggc aaggccccat tatatctgat gttgggggag cagatcttgg 960
gggagcccct tcagccccct cttccattcc ctcagggacc 1000
<210> 10
<211> 219
<212> PRT
<213> artificial sequence
<220>
<223> Interleukin-12 subunit alpha
<400> 10
Met Cys Pro Ala Arg Ser Leu Leu Leu Val Ala Thr Leu Val Leu Leu
1 5 10 15
Asp His Leu Ser Leu Ala Arg Asn Leu Pro Val Ala Thr Pro Asp Pro
20 25 30
Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val
35 40 45
Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys
50 55 60
Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser
65 70 75 80
Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys
85 90 95
Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala
100 105 110
Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr
115 120 125
Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys
130 135 140
Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu
145 150 155 160
Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr
165 170 175
Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys
180 185 190
Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr
195 200 205
Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser
210 215
<210> 11
<211> 328
<212> PRT
<213> artificial sequence
<220>
<223> Interleukin-12 subunit beta
<400> 11
Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu
1 5 10 15
Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val
20 25 30
Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln
50 55 60
Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys
65 70 75 80
Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val
85 90 95
Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp
100 105 110
Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe
115 120 125
Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp
130 135 140
Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg
145 150 155 160
Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser
165 170 175
Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu
180 185 190
Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile
195 200 205
Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr
210 215 220
Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn
225 230 235 240
Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp
245 250 255
Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr
260 265 270
Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg
275 280 285
Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala
290 295 300
Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser
305 310 315 320
Glu Trp Ala Ser Val Pro Cys Ser
325
<210> 12
<211> 1000
<212> DNA
<213> artificial sequence
<220>
<223> lck right homology
<400> 12
ggctgtggct gcagctcaca cccggaagat gactggatgg aaaacatcga tgtgtgtgag 60
aactgccatt atcccatagt cccactggat ggcaagggca cggtaagagg cgagacaggg 120
gccttggtga gggagttggg tagagaatgc aacccaggag aaagaaatga ccagcactac 180
aggcccttga aagaatagag tggccctctc ccctgaaata cagaaaggaa aagaggccca 240
gagaggggaa gggaatctcc taagatcaca cagaaagtag ttggtaaact cagggataac 300
atctaaccag gctggagagg ctgagagcag agcagggggg aagggggcca gggtctgacc 360
caatcttctg ctttctgacc ccaccctcat cccccactcc acagctgctc atccgaaatg 420
gctctgaggt gcgggaccca ctggttacct acgaaggctc caatccgccg gcttccccac 480
tgcaaggtga ccccaggcag cagggcctga aagacaaggc ctgcggatcc ctggctgttg 540
gcttccacct ctcccccacc tactttctcc ccggtcttgc cttccttgtc ccccaccctg 600
taactccagg cttcctgccg atcccagctc ggttctccct gatgcccctt gtctttacag 660
acaacctggt tatcgctctg cacagctatg agccctctca cgacggagat ctgggctttg 720
agaaggggga acagctccgc atcctggagc agtgagtccc tctccacctt gctctggcgg 780
agtccgtgag ggagcggcga tctccgcgac ccgcagccct cctgcggccc ttgaccagct 840
cggggtggcc gcccttggga caaaattcga ggctcagtat tgctgagcca gggttggggg 900
aggctggctt aaggggtgga ggggtctttg agggagggtc tcaggtcgac ggctgagcga 960
gccacactga cccacctccg tggcgcagga gcggcgagtg 1000
<210> 13
<211> 1992
<212> DNA
<213> artificial sequence
<220>
<223> apoptosis CAR
<400> 13
atggctttgc ctgtcactgc cttgctgctt ccacttgctc tgttgttgca cgccgcaaga 60
cccgaggtca agctccagga aagcggacca gggctggtgg cccctagtca gtcattgagc 120
gtcacttgca ccgtcagcgg cgtgtctctg cccgattacg gcgtgagctg gatcagacag 180
cccccaagga agggactgga gtggctgggc gtcatctggg ggagcgagac tacctactac 240
aacagcgccc tgaagagcag gctgaccatc attaaggaca actccaagtc ccaggtcttt 300
ctgaaaatga acagcctgca gactgatgac actgccatct actactgcgc caagcattac 360
tactacgggg gcagctacgc tatggactac tgggggcagg ggacctctgt cacagtgtca 420
agtggcggag gaggcagtgg cggaggggga agtgggggcg gcggcagcga catccagatg 480
acccagacaa catccagcct ctccgcctct ctgggcgaca gagtgacaat cagctgccgg 540
gccagtcagg acatcagcaa gtatctcaat tggtaccagc agaaaccaga cgggacagtg 600
aaattgctga tctaccacac atccaggctg cactcaggag tccccagcag gttttccggc 660
tccggctccg ggacagatta cagtctgacc atttccaacc tggagcagga ggatattgcc 720
acatactttt gccagcaagg caacactctg ccctatacct tcggcggagg cacaaaactg 780
gagattactc ggtcggatcc cgagcccaaa tctcctgaca aaactcacac atgcccaccg 840
tgcccagcac ctcccgtggc cggcccgtca gtgttcctct tccccccaaa acccaaggac 900
accctcatga tcgcccggac ccctgaggtc acatgcgtgg tggtggacgt gagccacgag 960
gaccctgagg tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca 1020
aagccgcggg aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg 1080
caccaggact ggctgaatgg caaggagtac aagtgcaagg tgtccaacaa agccctccca 1140
gcccccatcg agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac 1200
accctgcccc catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc 1260
aaaggcttct atcccagcga catcgccgtg gagtgggaga gcaatgggca accggagaac 1320
aactacaaga ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag 1380
ctcaccgtgg acaagagcag gtggcagcag gggaacgtgt tctcatgctc cgtgatgcat 1440
gaggccctgc acaatcacta tacccagaaa tctctgagtc tgagcccagg caagaaggat 1500
attttggggt ggctttgcct tcttcttttg ccaattccac taattgtttg ggtgaagaga 1560
aaggaagtac agaaaacatg cagaaagcac agaaaggaaa accaaggttc tcatgaatct 1620
ccaaccttaa atcctgaaac agtggcaata aatttatctg atgttgactt gagtaaatat 1680
atcaccacta ttgctggagt catgacacta agtcaagtta aaggctttgt tcgaaagaat 1740
ggtgtcaatg aagccaaaat agatgagatc aagaatgaca atgtccaaga cacagcagaa 1800
cagaaagttc aactgcttcg taattggcat caacttcatg gaaagaaaga agcgtatgac 1860
acattgattg cagatctcaa aaaagccaat ctttgtactc ttgcagagaa aattcagact 1920
atcatcctca aggacattac tagtgactca gaaaattcaa acttcagaaa tgaaatccag 1980
agcttggtcg aa 1992
<210> 14
<211> 1000
<212> DNA
<213> artificial sequence
<220>
<223> Lck left homology
<400> 14
ctcataacaa ttctatgagg taggaacagt tatttactct attttccaaa taaggaaact 60
gggctcgccc aaggttccac aactaacatg tgtgtattat tgagcattta atttacacca 120
gggaagcagg ttgtggtggt gtgcacctgt tgtccagcta tttaggaggc tgaggtgaaa 180
ggatcacttg aacggaggag ttcaaatttg caatgtgcta tgattgtgcc tgtgaacagc 240
tgctgcactc cagcctgggc aacatagtga gatcccttat ctaaaacatt ttttttaagt 300
aaataatcag gtgggcacgg tggctcacgc ctgtaatcca gcactttggg aggctgaggc 360
gggcggatca cctgaggtca ggagttcaag accagcctga ccaacatgga gaaacccgtc 420
tctactaaaa atacaaaatt agcttggcgt ggtggtgcat gcctgtaatc ccagctactc 480
gagaagctga ggcaggagaa ttgtttgaac ctgggaggtg gaggttgcgg tgagccgaga 540
tcgcaccatt gcactccagc ctgggcaaca agagtgaaat tgcatctcaa aaaaaaagaa 600
aaggaaataa tctataccag gcactccaag tggtgtgact gatattcaac aagtacctct 660
agtgtgacct taccattgat gaagaccaag attcttttgg attggtgctc acactgtgcc 720
agttaaatat tccgaacatt acccttgcct gtgggcttcc agtgcctgac cttgatgtcc 780
tttcacccat caacccgtag ggatgaccaa cccggaggtg attcagaacc tggagcgagg 840
ctaccgcatg gtgcgccctg acaactgtcc agaggagctg taccaactca tgaggctgtg 900
ctggaaggag cgcccagagg accggcccac ctttgactac ctgcgcagtg tgctggagga 960
cttcttcacg gccacagagg gccagtacca gcctcagcct 1000
<210> 15
<211> 1000
<212> DNA
<213> artificial sequence
<220>
<223> lck right homology
<400> 15
gaggccttga gaggccctgg ggttctcccc ctttctctcc agcctgactt ggggagatgg 60
agttcttgtg ccatagtcac atggcctatg cacatatgga ctctgcacat gaatcccacc 120
cacatgtgac acatatgcac cttgtgtctg tacacgtgtc ctgtagttgc gtggactctg 180
cacatgtctt gtacatgtgt agcctgtgca tgtatgtctt ggacactgta caaggtaccc 240
ctttctggct ctcccatttc ctgagaccac agagagaggg gagaagcctg ggattgacag 300
aagcttctgc ccacctactt ttctttcctc agatcatcca gaagttcctc aagggccagg 360
actttatcta atacctctgt gtgctcctcc ttggtgcctg gcctggcaca catcaggagt 420
tcaataaatg tctgttgatg actgttgtac atctctttgc tgtccactct ttgtgggtgg 480
gcagtggggg ttaagaaaat ggtaattagg tcaccctgag ttggggtgaa agatgggatg 540
agtggatgtc tggaggctct gcagacccct tcaaatggga cagtgctcct cacccctccc 600
caaaggattc agggtgactc ctacctggaa tcccttaggg aatgggtgcg tcaaaggacc 660
ttcctcccca ttataaaagg gcaacagcat tttttactga ttcaagggct atatttgacc 720
tcagattttg tttttttaag gctagtcaaa tgaagcggcg ggaatggagg aggaacaaat 780
aaatctgtaa ctatcctcag attttttttt ttttttgaga ctgggtctca ctttttcatc 840
caggctggag tgcagtcgca tgatcacggc tcactgtagc ctcaacctct ccagctcaaa 900
tgctcctcct gtctcagcct cccgagtacc tgggactact ttcttgaggc caggaattca 960
agaacagagt aagatcctgg tctccaaaaa aagttttaaa 1000
<210> 16
<211> 936
<212> PRT
<213> artificial sequence
<220>
<223> TALEN TRAC
<400> 16
Met Gly Asp Pro Lys Lys Lys Arg Lys Val Ile Asp Tyr Pro Tyr Asp
1 5 10 15
Val Pro Asp Tyr Ala Ile Asp Ile Ala Asp Leu Arg Thr Leu Gly Tyr
20 25 30
Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys Val Arg Ser Thr Val
35 40 45
Ala Gln His His Glu Ala Leu Val Gly His Gly Phe Thr His Ala His
50 55 60
Ile Val Ala Leu Ser Gln His Pro Ala Ala Leu Gly Thr Val Ala Val
65 70 75 80
Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro Glu Ala Thr His Glu Ala
85 90 95
Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala Arg Ala Leu Glu Ala
100 105 110
Leu Leu Thr Val Ala Gly Glu Leu Arg Gly Pro Pro Leu Gln Leu Asp
115 120 125
Thr Gly Gln Leu Leu Lys Ile Ala Lys Arg Gly Gly Val Thr Ala Val
130 135 140
Glu Ala Val His Ala Trp Arg Asn Ala Leu Thr Gly Ala Pro Leu Asn
145 150 155 160
Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys
165 170 175
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
180 185 190
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly
195 200 205
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
210 215 220
Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn
225 230 235 240
Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
245 250 255
Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala
260 265 270
Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
275 280 285
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala
290 295 300
Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
305 310 315 320
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val
325 330 335
Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val
340 345 350
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
355 360 365
Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu
370 375 380
Thr Val Gln Ala Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
385 390 395 400
Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala
405 410 415
Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly
420 425 430
Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys
435 440 445
Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val Leu Cys Gln Ala
450 455 460
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly
465 470 475 480
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
485 490 495
Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn
500 505 510
Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val
515 520 525
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
530 535 540
Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
545 550 555 560
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala
565 570 575
Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala
580 585 590
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
595 600 605
Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val
610 615 620
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
625 630 635 640
Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu
645 650 655
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
660 665 670
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Arg Pro Ala
675 680 685
Leu Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala
690 695 700
Ala Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys Leu Gly Gly Arg
705 710 715 720
Pro Ala Leu Asp Ala Val Lys Lys Gly Leu Gly Asp Pro Ile Ser Arg
725 730 735
Ser Gln Leu Val Lys Ser Glu Leu Glu Glu Lys Lys Ser Glu Leu Arg
740 745 750
His Lys Leu Lys Tyr Val Pro His Glu Tyr Ile Glu Leu Ile Glu Ile
755 760 765
Ala Arg Asn Ser Thr Gln Asp Arg Ile Leu Glu Met Lys Val Met Glu
770 775 780
Phe Phe Met Lys Val Tyr Gly Tyr Arg Gly Lys His Leu Gly Gly Ser
785 790 795 800
Arg Lys Pro Asp Gly Ala Ile Tyr Thr Val Gly Ser Pro Ile Asp Tyr
805 810 815
Gly Val Ile Val Asp Thr Lys Ala Tyr Ser Gly Gly Tyr Asn Leu Pro
820 825 830
Ile Gly Gln Ala Asp Glu Met Gln Arg Tyr Val Glu Glu Asn Gln Thr
835 840 845
Arg Asn Lys His Ile Asn Pro Asn Glu Trp Trp Lys Val Tyr Pro Ser
850 855 860
Ser Val Thr Glu Phe Lys Phe Leu Phe Val Ser Gly His Phe Lys Gly
865 870 875 880
Asn Tyr Lys Ala Gln Leu Thr Arg Leu Asn His Ile Thr Asn Cys Asn
885 890 895
Gly Ala Val Leu Ser Val Glu Glu Leu Leu Ile Gly Gly Glu Met Ile
900 905 910
Lys Ala Gly Thr Leu Thr Leu Glu Glu Val Arg Arg Lys Phe Asn Asn
915 920 925
Gly Glu Ile Asn Phe Ala Ala Asp
930 935
<210> 17
<211> 942
<212> PRT
<213> artificial sequence
<220>
<223> TALEN TRAC
<400> 17
Met Gly Asp Pro Lys Lys Lys Arg Lys Val Ile Asp Lys Glu Thr Ala
1 5 10 15
Ala Ala Lys Phe Glu Arg Gln His Met Asp Ser Ile Asp Ile Ala Asp
20 25 30
Leu Arg Thr Leu Gly Tyr Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro
35 40 45
Lys Val Arg Ser Thr Val Ala Gln His His Glu Ala Leu Val Gly His
50 55 60
Gly Phe Thr His Ala His Ile Val Ala Leu Ser Gln His Pro Ala Ala
65 70 75 80
Leu Gly Thr Val Ala Val Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro
85 90 95
Glu Ala Thr His Glu Ala Ile Val Gly Val Gly Lys Gln Trp Ser Gly
100 105 110
Ala Arg Ala Leu Glu Ala Leu Leu Thr Val Ala Gly Glu Leu Arg Gly
115 120 125
Pro Pro Leu Gln Leu Asp Thr Gly Gln Leu Leu Lys Ile Ala Lys Arg
130 135 140
Gly Gly Val Thr Ala Val Glu Ala Val His Ala Trp Arg Asn Ala Leu
145 150 155 160
Thr Gly Ala Pro Leu Asn Leu Thr Pro Glu Gln Val Val Ala Ile Ala
165 170 175
Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
180 185 190
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
195 200 205
Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
210 215 220
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val
225 230 235 240
Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val
245 250 255
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
260 265 270
Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu
275 280 285
Thr Val Gln Ala Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
290 295 300
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala
305 310 315 320
Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly
325 330 335
Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys
340 345 350
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
355 360 365
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly
370 375 380
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
385 390 395 400
Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn
405 410 415
Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
420 425 430
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
435 440 445
Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
450 455 460
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
465 470 475 480
Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
485 490 495
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val
500 505 510
Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val
515 520 525
Gln Ala Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
530 535 540
Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu
545 550 555 560
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
565 570 575
Pro Glu Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala
580 585 590
Leu Glu Thr Val Gln Ala Leu Leu Pro Val Leu Cys Gln Ala His Gly
595 600 605
Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys
610 615 620
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
625 630 635 640
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly
645 650 655
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
660 665 670
Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn
675 680 685
Gly Gly Gly Arg Pro Ala Leu Glu Ser Ile Val Ala Gln Leu Ser Arg
690 695 700
Pro Asp Pro Ala Leu Ala Ala Leu Thr Asn Asp His Leu Val Ala Leu
705 710 715 720
Ala Cys Leu Gly Gly Arg Pro Ala Leu Asp Ala Val Lys Lys Gly Leu
725 730 735
Gly Asp Pro Ile Ser Arg Ser Gln Leu Val Lys Ser Glu Leu Glu Glu
740 745 750
Lys Lys Ser Glu Leu Arg His Lys Leu Lys Tyr Val Pro His Glu Tyr
755 760 765
Ile Glu Leu Ile Glu Ile Ala Arg Asn Ser Thr Gln Asp Arg Ile Leu
770 775 780
Glu Met Lys Val Met Glu Phe Phe Met Lys Val Tyr Gly Tyr Arg Gly
785 790 795 800
Lys His Leu Gly Gly Ser Arg Lys Pro Asp Gly Ala Ile Tyr Thr Val
805 810 815
Gly Ser Pro Ile Asp Tyr Gly Val Ile Val Asp Thr Lys Ala Tyr Ser
820 825 830
Gly Gly Tyr Asn Leu Pro Ile Gly Gln Ala Asp Glu Met Gln Arg Tyr
835 840 845
Val Glu Glu Asn Gln Thr Arg Asn Lys His Ile Asn Pro Asn Glu Trp
850 855 860
Trp Lys Val Tyr Pro Ser Ser Val Thr Glu Phe Lys Phe Leu Phe Val
865 870 875 880
Ser Gly His Phe Lys Gly Asn Tyr Lys Ala Gln Leu Thr Arg Leu Asn
885 890 895
His Ile Thr Asn Cys Asn Gly Ala Val Leu Ser Val Glu Glu Leu Leu
900 905 910
Ile Gly Gly Glu Met Ile Lys Ala Gly Thr Leu Thr Leu Glu Glu Val
915 920 925
Arg Arg Lys Phe Asn Asn Gly Glu Ile Asn Phe Ala Ala Asp
930 935 940
<210> 18
<211> 913
<212> PRT
<213> artificial sequence
<220>
<223> TALEN CD25
<400> 18
Met Gly Asp Pro Lys Lys Lys Arg Lys Val Ile Asp Tyr Pro Tyr Asp
1 5 10 15
Val Pro Asp Tyr Ala Ile Asp Ile Ala Asp Leu Arg Thr Leu Gly Tyr
20 25 30
Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys Val Arg Ser Thr Val
35 40 45
Ala Gln His His Glu Ala Leu Val Gly His Gly Phe Thr His Ala His
50 55 60
Ile Val Ala Leu Ser Gln His Pro Ala Ala Leu Gly Thr Val Ala Val
65 70 75 80
Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro Glu Ala Thr His Glu Ala
85 90 95
Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala Arg Ala Leu Glu Ala
100 105 110
Leu Leu Thr Val Ala Gly Glu Leu Arg Gly Pro Pro Leu Gln Leu Asp
115 120 125
Thr Gly Gln Leu Leu Lys Ile Ala Lys Arg Gly Gly Val Thr Ala Val
130 135 140
Glu Ala Val His Ala Trp Arg Asn Ala Leu Thr Gly Ala Pro Leu Asn
145 150 155 160
Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys
165 170 175
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
180 185 190
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly
195 200 205
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
210 215 220
Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn
225 230 235 240
Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
245 250 255
Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala
260 265 270
Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
275 280 285
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
290 295 300
Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
305 310 315 320
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
325 330 335
Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val
340 345 350
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln
355 360 365
Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu
370 375 380
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
385 390 395 400
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala
405 410 415
Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly
420 425 430
Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys
435 440 445
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
450 455 460
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly
465 470 475 480
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
485 490 495
Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn
500 505 510
Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
515 520 525
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
530 535 540
Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
545 550 555 560
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
565 570 575
Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
580 585 590
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
595 600 605
Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val
610 615 620
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
625 630 635 640
Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu
645 650 655
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
660 665 670
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Arg Pro Ala
675 680 685
Leu Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro Ser Gly Ser
690 695 700
Gly Ser Gly Gly Asp Pro Ile Ser Arg Ser Gln Leu Val Lys Ser Glu
705 710 715 720
Leu Glu Glu Lys Lys Ser Glu Leu Arg His Lys Leu Lys Tyr Val Pro
725 730 735
His Glu Tyr Ile Glu Leu Ile Glu Ile Ala Arg Asn Ser Thr Gln Asp
740 745 750
Arg Ile Leu Glu Met Lys Val Met Glu Phe Phe Met Lys Val Tyr Gly
755 760 765
Tyr Arg Gly Lys His Leu Gly Gly Ser Arg Lys Pro Asp Gly Ala Ile
770 775 780
Tyr Thr Val Gly Ser Pro Ile Asp Tyr Gly Val Ile Val Asp Thr Lys
785 790 795 800
Ala Tyr Ser Gly Gly Tyr Asn Leu Pro Ile Gly Gln Ala Asp Glu Met
805 810 815
Gln Arg Tyr Val Glu Glu Asn Gln Thr Arg Asn Lys His Ile Asn Pro
820 825 830
Asn Glu Trp Trp Lys Val Tyr Pro Ser Ser Val Thr Glu Phe Lys Phe
835 840 845
Leu Phe Val Ser Gly His Phe Lys Gly Asn Tyr Lys Ala Gln Leu Thr
850 855 860
Arg Leu Asn His Ile Thr Asn Cys Asn Gly Ala Val Leu Ser Val Glu
865 870 875 880
Glu Leu Leu Ile Gly Gly Glu Met Ile Lys Ala Gly Thr Leu Thr Leu
885 890 895
Glu Glu Val Arg Arg Lys Phe Asn Asn Gly Glu Ile Asn Phe Ala Ala
900 905 910
Asp
<210> 19
<211> 913
<212> PRT
<213> artificial sequence
<220>
<223> TALEN CD25
<400> 19
Met Gly Asp Pro Lys Lys Lys Arg Lys Val Ile Asp Tyr Pro Tyr Asp
1 5 10 15
Val Pro Asp Tyr Ala Ile Asp Ile Ala Asp Leu Arg Thr Leu Gly Tyr
20 25 30
Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys Val Arg Ser Thr Val
35 40 45
Ala Gln His His Glu Ala Leu Val Gly His Gly Phe Thr His Ala His
50 55 60
Ile Val Ala Leu Ser Gln His Pro Ala Ala Leu Gly Thr Val Ala Val
65 70 75 80
Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro Glu Ala Thr His Glu Ala
85 90 95
Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala Arg Ala Leu Glu Ala
100 105 110
Leu Leu Thr Val Ala Gly Glu Leu Arg Gly Pro Pro Leu Gln Leu Asp
115 120 125
Thr Gly Gln Leu Leu Lys Ile Ala Lys Arg Gly Gly Val Thr Ala Val
130 135 140
Glu Ala Val His Ala Trp Arg Asn Ala Leu Thr Gly Ala Pro Leu Asn
145 150 155 160
Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys
165 170 175
Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val Leu Cys Gln Ala
180 185 190
His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly
195 200 205
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
210 215 220
Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn
225 230 235 240
Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val
245 250 255
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
260 265 270
Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
275 280 285
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
290 295 300
Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
305 310 315 320
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val
325 330 335
Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val
340 345 350
Gln Ala Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln
355 360 365
Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu
370 375 380
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
385 390 395 400
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala
405 410 415
Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly
420 425 430
Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys
435 440 445
Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val Leu Cys Gln Ala
450 455 460
His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn Ile Gly
465 470 475 480
Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val Leu Cys
485 490 495
Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn
500 505 510
Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
515 520 525
Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala
530 535 540
Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu
545 550 555 560
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
565 570 575
Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
580 585 590
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
595 600 605
Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val
610 615 620
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
625 630 635 640
Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu
645 650 655
Thr Val Gln Ala Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
660 665 670
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Arg Pro Ala
675 680 685
Leu Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro Ser Gly Ser
690 695 700
Gly Ser Gly Gly Asp Pro Ile Ser Arg Ser Gln Leu Val Lys Ser Glu
705 710 715 720
Leu Glu Glu Lys Lys Ser Glu Leu Arg His Lys Leu Lys Tyr Val Pro
725 730 735
His Glu Tyr Ile Glu Leu Ile Glu Ile Ala Arg Asn Ser Thr Gln Asp
740 745 750
Arg Ile Leu Glu Met Lys Val Met Glu Phe Phe Met Lys Val Tyr Gly
755 760 765
Tyr Arg Gly Lys His Leu Gly Gly Ser Arg Lys Pro Asp Gly Ala Ile
770 775 780
Tyr Thr Val Gly Ser Pro Ile Asp Tyr Gly Val Ile Val Asp Thr Lys
785 790 795 800
Ala Tyr Ser Gly Gly Tyr Asn Leu Pro Ile Gly Gln Ala Asp Glu Met
805 810 815
Gln Arg Tyr Val Glu Glu Asn Gln Thr Arg Asn Lys His Ile Asn Pro
820 825 830
Asn Glu Trp Trp Lys Val Tyr Pro Ser Ser Val Thr Glu Phe Lys Phe
835 840 845
Leu Phe Val Ser Gly His Phe Lys Gly Asn Tyr Lys Ala Gln Leu Thr
850 855 860
Arg Leu Asn His Ile Thr Asn Cys Asn Gly Ala Val Leu Ser Val Glu
865 870 875 880
Glu Leu Leu Ile Gly Gly Glu Met Ile Lys Ala Gly Thr Leu Thr Leu
885 890 895
Glu Glu Val Arg Arg Lys Phe Asn Asn Gly Glu Ile Asn Phe Ala Ala
900 905 910
Asp
<210> 20
<211> 936
<212> PRT
<213> artificial sequence
<220>
<223> TALEN PD1
<400> 20
Met Gly Asp Pro Lys Lys Lys Arg Lys Val Ile Asp Tyr Pro Tyr Asp
1 5 10 15
Val Pro Asp Tyr Ala Ile Asp Ile Ala Asp Leu Arg Thr Leu Gly Tyr
20 25 30
Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys Val Arg Ser Thr Val
35 40 45
Ala Gln His His Glu Ala Leu Val Gly His Gly Phe Thr His Ala His
50 55 60
Ile Val Ala Leu Ser Gln His Pro Ala Ala Leu Gly Thr Val Ala Val
65 70 75 80
Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro Glu Ala Thr His Glu Ala
85 90 95
Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala Arg Ala Leu Glu Ala
100 105 110
Leu Leu Thr Val Ala Gly Glu Leu Arg Gly Pro Pro Leu Gln Leu Asp
115 120 125
Thr Gly Gln Leu Leu Lys Ile Ala Lys Arg Gly Gly Val Thr Ala Val
130 135 140
Glu Ala Val His Ala Trp Arg Asn Ala Leu Thr Gly Ala Pro Leu Asn
145 150 155 160
Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Lys Leu Gly Gly Lys
165 170 175
Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val Leu Cys Gln Ala
180 185 190
His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly
195 200 205
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
210 215 220
Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His
225 230 235 240
Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
245 250 255
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
260 265 270
Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
275 280 285
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala
290 295 300
Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
305 310 315 320
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
325 330 335
Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val
340 345 350
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln
355 360 365
Gln Val Val Ala Ile Ala Ser Tyr Lys Gly Gly Lys Gln Ala Leu Glu
370 375 380
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
385 390 395 400
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala
405 410 415
Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly
420 425 430
Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys
435 440 445
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
450 455 460
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly
465 470 475 480
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
485 490 495
Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn
500 505 510
Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
515 520 525
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
530 535 540
Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
545 550 555 560
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala
565 570 575
Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
580 585 590
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val
595 600 605
Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val
610 615 620
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
625 630 635 640
Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu
645 650 655
Thr Val Gln Ala Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
660 665 670
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Arg Pro Ala
675 680 685
Leu Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala
690 695 700
Ala Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys Leu Gly Gly Arg
705 710 715 720
Pro Ala Leu Asp Ala Val Lys Lys Gly Leu Gly Asp Pro Ile Ser Arg
725 730 735
Ser Gln Leu Val Lys Ser Glu Leu Glu Glu Lys Lys Ser Glu Leu Arg
740 745 750
His Lys Leu Lys Tyr Val Pro His Glu Tyr Ile Glu Leu Ile Glu Ile
755 760 765
Ala Arg Asn Ser Thr Gln Asp Arg Ile Leu Glu Met Lys Val Met Glu
770 775 780
Phe Phe Met Lys Val Tyr Gly Tyr Arg Gly Lys His Leu Gly Gly Ser
785 790 795 800
Arg Lys Pro Asp Gly Ala Ile Tyr Thr Val Gly Ser Pro Ile Asp Tyr
805 810 815
Gly Val Ile Val Asp Thr Lys Ala Tyr Ser Gly Gly Tyr Asn Leu Pro
820 825 830
Ile Gly Gln Ala Asp Glu Met Gln Arg Tyr Val Glu Glu Asn Gln Thr
835 840 845
Arg Asn Lys His Ile Asn Pro Asn Glu Trp Trp Lys Val Tyr Pro Ser
850 855 860
Ser Val Thr Glu Phe Lys Phe Leu Phe Val Ser Gly His Phe Lys Gly
865 870 875 880
Asn Tyr Lys Ala Gln Leu Thr Arg Leu Asn His Ile Thr Asn Cys Asn
885 890 895
Gly Ala Val Leu Ser Val Glu Glu Leu Leu Ile Gly Gly Glu Met Ile
900 905 910
Lys Ala Gly Thr Leu Thr Leu Glu Glu Val Arg Arg Lys Phe Asn Asn
915 920 925
Gly Glu Ile Asn Phe Ala Ala Asp
930 935
<210> 21
<211> 941
<212> PRT
<213> artificial sequence
<220>
<223> TALEN PD1
<400> 21
Met Gly Asp Pro Lys Lys Lys Arg Lys Val Ile Asp Lys Glu Thr Ala
1 5 10 15
Ala Ala Lys Phe Glu Arg Gln His Met Asp Ser Ile Asp Ile Ala Asp
20 25 30
Leu Arg Thr Leu Gly Tyr Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro
35 40 45
Lys Val Arg Ser Thr Val Ala Gln His His Glu Ala Leu Val Gly His
50 55 60
Gly Phe Thr His Ala His Ile Val Ala Leu Ser Gln His Pro Ala Ala
65 70 75 80
Leu Gly Thr Val Ala Val Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro
85 90 95
Glu Ala Thr His Glu Ala Ile Val Gly Val Gly Lys Gln Trp Ser Gly
100 105 110
Ala Arg Ala Leu Glu Ala Leu Leu Thr Val Ala Gly Glu Leu Arg Gly
115 120 125
Pro Pro Leu Gln Leu Asp Thr Gly Gln Leu Leu Lys Ile Ala Lys Arg
130 135 140
Gly Gly Val Thr Ala Val Glu Ala Val His Ala Trp Arg Asn Ala Leu
145 150 155 160
Thr Gly Ala Pro Leu Asn Leu Thr Pro Glu Gln Val Val Ala Ile Ala
165 170 175
Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
180 185 190
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
195 200 205
Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
210 215 220
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val
225 230 235 240
Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val
245 250 255
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln
260 265 270
Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu
275 280 285
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
290 295 300
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala
305 310 315 320
Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly
325 330 335
Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys
340 345 350
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
355 360 365
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly
370 375 380
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
385 390 395 400
Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn
405 410 415
Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val
420 425 430
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
435 440 445
Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
450 455 460
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala
465 470 475 480
Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
485 490 495
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
500 505 510
Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val
515 520 525
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln
530 535 540
Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu
545 550 555 560
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
565 570 575
Pro Glu Gln Val Val Ala Ile Ala Ser Asn Gly Gly Lys Gln Ala Leu
580 585 590
Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu
595 600 605
Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln
610 615 620
Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His
625 630 635 640
Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly Gly
645 650 655
Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln
660 665 670
Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly
675 680 685
Gly Gly Arg Pro Ala Leu Glu Ser Ile Val Ala Gln Leu Ser Arg Pro
690 695 700
Asp Pro Ala Leu Ala Ala Leu Thr Asn Asp His Leu Val Ala Leu Ala
705 710 715 720
Cys Leu Gly Gly Arg Pro Ala Leu Asp Ala Val Lys Lys Gly Leu Gly
725 730 735
Asp Pro Ile Ser Arg Ser Gln Leu Val Lys Ser Glu Leu Glu Glu Lys
740 745 750
Lys Ser Glu Leu Arg His Lys Leu Lys Tyr Val Pro His Glu Tyr Ile
755 760 765
Glu Leu Ile Glu Ile Ala Arg Asn Ser Thr Gln Asp Arg Ile Leu Glu
770 775 780
Met Lys Val Met Glu Phe Phe Met Lys Val Tyr Gly Tyr Arg Gly Lys
785 790 795 800
His Leu Gly Gly Ser Arg Lys Pro Asp Gly Ala Ile Tyr Thr Val Gly
805 810 815
Ser Pro Ile Asp Tyr Gly Val Ile Val Asp Thr Lys Ala Tyr Ser Gly
820 825 830
Gly Tyr Asn Leu Pro Ile Gly Gln Ala Asp Glu Met Gln Arg Tyr Val
835 840 845
Glu Glu Asn Gln Thr Arg Asn Lys His Ile Asn Pro Asn Glu Trp Trp
850 855 860
Lys Val Tyr Pro Ser Ser Val Thr Glu Phe Lys Phe Leu Phe Val Ser
865 870 875 880
Gly His Phe Lys Gly Asn Tyr Lys Ala Gln Leu Thr Arg Leu Asn His
885 890 895
Ile Thr Asn Cys Asn Gly Ala Val Leu Ser Val Glu Glu Leu Leu Ile
900 905 910
Gly Gly Glu Met Ile Lys Ala Gly Thr Leu Thr Leu Glu Glu Val Arg
915 920 925
Arg Lys Phe Asn Asn Gly Glu Ile Asn Phe Ala Ala Asp
930 935 940
<210> 22
<211> 2814
<212> DNA
<213> artificial sequence
<220>
<223> TALEN TRAC pCLS11370
<400> 22
atgggcgatc ctaaaaagaa acgtaaggtc atcgattacc catacgatgt tccagattac 60
gctatcgata tcgccgatct acgcacgctc ggctacagcc agcagcaaca ggagaagatc 120
aaaccgaagg ttcgttcgac agtggcgcag caccacgagg cactggtcgg ccacgggttt 180
acacacgcgc acatcgttgc gttaagccaa cacccggcag cgttagggac cgtcgctgtc 240
aagtatcagg acatgatcgc agcgttgcca gaggcgacac acgaagcgat cgttggcgtc 300
ggcaaacagt ggtccggcgc acgcgctctg gaggccttgc tcacggtggc gggagagttg 360
agaggtccac cgttacagtt ggacacaggc caacttctca agattgcaaa acgtggcggc 420
gtgaccgcag tggaggcagt gcatgcatgg cgcaatgcac tgacgggtgc cccgctcaac 480
ttgacccccc agcaggtggt ggccatcgcc agcaatggcg gtggcaagca ggcgctggag 540
acggtccagc ggctgttgcc ggtgctgtgc caggcccacg gcttgacccc ccagcaggtg 600
gtggccatcg ccagcaataa tggtggcaag caggcgctgg agacggtcca gcggctgttg 660
ccggtgctgt gccaggccca cggcttgacc ccccagcagg tggtggccat cgccagcaat 720
ggcggtggca agcaggcgct ggagacggtc cagcggctgt tgccggtgct gtgccaggcc 780
cacggcttga ccccggagca ggtggtggcc atcgccagcc acgatggcgg caagcaggcg 840
ctggagacgg tccagcggct gttgccggtg ctgtgccagg cccacggctt gaccccggag 900
caggtggtgg ccatcgccag ccacgatggc ggcaagcagg cgctggagac ggtccagcgg 960
ctgttgccgg tgctgtgcca ggcccacggc ttgaccccgg agcaggtggt ggccatcgcc 1020
agccacgatg gcggcaagca ggcgctggag acggtccagc ggctgttgcc ggtgctgtgc 1080
caggcccacg gcttgacccc ggagcaggtg gtggccatcg ccagcaatat tggtggcaag 1140
caggcgctgg agacggtgca ggcgctgttg ccggtgctgt gccaggccca cggcttgacc 1200
ccggagcagg tggtggccat cgccagccac gatggcggca agcaggcgct ggagacggtc 1260
cagcggctgt tgccggtgct gtgccaggcc cacggcttga ccccggagca ggtggtggcc 1320
atcgccagca atattggtgg caagcaggcg ctggagacgg tgcaggcgct gttgccggtg 1380
ctgtgccagg cccacggctt gaccccccag caggtggtgg ccatcgccag caataatggt 1440
ggcaagcagg cgctggagac ggtccagcgg ctgttgccgg tgctgtgcca ggcccacggc 1500
ttgaccccgg agcaggtggt ggccatcgcc agcaatattg gtggcaagca ggcgctggag 1560
acggtgcagg cgctgttgcc ggtgctgtgc caggcccacg gcttgacccc ccagcaggtg 1620
gtggccatcg ccagcaatgg cggtggcaag caggcgctgg agacggtcca gcggctgttg 1680
ccggtgctgt gccaggccca cggcttgacc ccggagcagg tggtggccat cgccagcaat 1740
attggtggca agcaggcgct ggagacggtg caggcgctgt tgccggtgct gtgccaggcc 1800
cacggcttga ccccccagca ggtggtggcc atcgccagca atggcggtgg caagcaggcg 1860
ctggagacgg tccagcggct gttgccggtg ctgtgccagg cccacggctt gaccccggag 1920
caggtggtgg ccatcgccag ccacgatggc ggcaagcagg cgctggagac ggtccagcgg 1980
ctgttgccgg tgctgtgcca ggcccacggc ttgacccctc agcaggtggt ggccatcgcc 2040
agcaatggcg gcggcaggcc ggcgctggag agcattgttg cccagttatc tcgccctgat 2100
ccggcgttgg ccgcgttgac caacgaccac ctcgtcgcct tggcctgcct cggcgggcgt 2160
cctgcgctgg atgcagtgaa aaagggattg ggggatccta tcagccgttc ccagctggtg 2220
aagtccgagc tggaggagaa gaaatccgag ttgaggcaca agctgaagta cgtgccccac 2280
gagtacatcg agctgatcga gatcgcccgg aacagcaccc aggaccgtat cctggagatg 2340
aaggtgatgg agttcttcat gaaggtgtac ggctacaggg gcaagcacct gggcggctcc 2400
aggaagcccg acggcgccat ctacaccgtg ggctccccca tcgactacgg cgtgatcgtg 2460
gacaccaagg cctactccgg cggctacaac ctgcccatcg gccaggccga cgaaatgcag 2520
aggtacgtgg aggagaacca gaccaggaac aagcacatca accccaacga gtggtggaag 2580
gtgtacccct ccagcgtgac cgagttcaag ttcctgttcg tgtccggcca cttcaagggc 2640
aactacaagg cccagctgac caggctgaac cacatcacca actgcaacgg cgccgtgctg 2700
tccgtggagg agctcctgat cggcggcgag atgatcaagg ccggcaccct gaccctggag 2760
gaggtgagga ggaagttcaa caacggcgag atcaacttcg cggccgactg ataa 2814
<210> 23
<211> 2832
<212> DNA
<213> artificial sequence
<220>
<223> TALEN TRAC pCLS11369
<400> 23
atgggcgatc ctaaaaagaa acgtaaggtc atcgataagg agaccgccgc tgccaagttc 60
gagagacagc acatggacag catcgatatc gccgatctac gcacgctcgg ctacagccag 120
cagcaacagg agaagatcaa accgaaggtt cgttcgacag tggcgcagca ccacgaggca 180
ctggtcggcc acgggtttac acacgcgcac atcgttgcgt taagccaaca cccggcagcg 240
ttagggaccg tcgctgtcaa gtatcaggac atgatcgcag cgttgccaga ggcgacacac 300
gaagcgatcg ttggcgtcgg caaacagtgg tccggcgcac gcgctctgga ggccttgctc 360
acggtggcgg gagagttgag aggtccaccg ttacagttgg acacaggcca acttctcaag 420
attgcaaaac gtggcggcgt gaccgcagtg gaggcagtgc atgcatggcg caatgcactg 480
acgggtgccc cgctcaactt gaccccggag caggtggtgg ccatcgccag ccacgatggc 540
ggcaagcagg cgctggagac ggtccagcgg ctgttgccgg tgctgtgcca ggcccacggc 600
ttgacccccc agcaggtggt ggccatcgcc agcaatggcg gtggcaagca ggcgctggag 660
acggtccagc ggctgttgcc ggtgctgtgc caggcccacg gcttgacccc ggagcaggtg 720
gtggccatcg ccagccacga tggcggcaag caggcgctgg agacggtcca gcggctgttg 780
ccggtgctgt gccaggccca cggcttgacc ccggagcagg tggtggccat cgccagcaat 840
attggtggca agcaggcgct ggagacggtg caggcgctgt tgccggtgct gtgccaggcc 900
cacggcttga ccccccagca ggtggtggcc atcgccagca ataatggtgg caagcaggcg 960
ctggagacgg tccagcggct gttgccggtg ctgtgccagg cccacggctt gaccccggag 1020
caggtggtgg ccatcgccag ccacgatggc ggcaagcagg cgctggagac ggtccagcgg 1080
ctgttgccgg tgctgtgcca ggcccacggc ttgacccccc agcaggtggt ggccatcgcc 1140
agcaatggcg gtggcaagca ggcgctggag acggtccagc ggctgttgcc ggtgctgtgc 1200
caggcccacg gcttgacccc ccagcaggtg gtggccatcg ccagcaataa tggtggcaag 1260
caggcgctgg agacggtcca gcggctgttg ccggtgctgt gccaggccca cggcttgacc 1320
ccccagcagg tggtggccat cgccagcaat aatggtggca agcaggcgct ggagacggtc 1380
cagcggctgt tgccggtgct gtgccaggcc cacggcttga ccccccagca ggtggtggcc 1440
atcgccagca atggcggtgg caagcaggcg ctggagacgg tccagcggct gttgccggtg 1500
ctgtgccagg cccacggctt gaccccggag caggtggtgg ccatcgccag caatattggt 1560
ggcaagcagg cgctggagac ggtgcaggcg ctgttgccgg tgctgtgcca ggcccacggc 1620
ttgaccccgg agcaggtggt ggccatcgcc agccacgatg gcggcaagca ggcgctggag 1680
acggtccagc ggctgttgcc ggtgctgtgc caggcccacg gcttgacccc ggagcaggtg 1740
gtggccatcg ccagcaatat tggtggcaag caggcgctgg agacggtgca ggcgctgttg 1800
ccggtgctgt gccaggccca cggcttgacc ccggagcagg tggtggccat cgccagccac 1860
gatggcggca agcaggcgct ggagacggtc cagcggctgt tgccggtgct gtgccaggcc 1920
cacggcttga ccccccagca ggtggtggcc atcgccagca ataatggtgg caagcaggcg 1980
ctggagacgg tccagcggct gttgccggtg ctgtgccagg cccacggctt gacccctcag 2040
caggtggtgg ccatcgccag caatggcggc ggcaggccgg cgctggagag cattgttgcc 2100
cagttatctc gccctgatcc ggcgttggcc gcgttgacca acgaccacct cgtcgccttg 2160
gcctgcctcg gcgggcgtcc tgcgctggat gcagtgaaaa agggattggg ggatcctatc 2220
agccgttccc agctggtgaa gtccgagctg gaggagaaga aatccgagtt gaggcacaag 2280
ctgaagtacg tgccccacga gtacatcgag ctgatcgaga tcgcccggaa cagcacccag 2340
gaccgtatcc tggagatgaa ggtgatggag ttcttcatga aggtgtacgg ctacaggggc 2400
aagcacctgg gcggctccag gaagcccgac ggcgccatct acaccgtggg ctcccccatc 2460
gactacggcg tgatcgtgga caccaaggcc tactccggcg gctacaacct gcccatcggc 2520
caggccgacg aaatgcagag gtacgtggag gagaaccaga ccaggaacaa gcacatcaac 2580
cccaacgagt ggtggaaggt gtacccctcc agcgtgaccg agttcaagtt cctgttcgtg 2640
tccggccact tcaagggcaa ctacaaggcc cagctgacca ggctgaacca catcaccaac 2700
tgcaacggcg ccgtgctgtc cgtggaggag ctcctgatcg gcggcgagat gatcaaggcc 2760
ggcaccctga ccctggagga ggtgaggagg aagttcaaca acggcgagat caacttcgcg 2820
gccgactgat aa 2832
<210> 24
<211> 2745
<212> DNA
<213> artificial sequence
<220>
<223> TALEN CD25 pCLS30480
<400> 24
atgggcgatc ctaaaaagaa acgtaaggtc atcgattacc catacgatgt tccagattac 60
gctatcgata tcgccgatct acgcacgctc ggctacagcc agcagcaaca ggagaagatc 120
aaaccgaagg ttcgttcgac agtggcgcag caccacgagg cactggtcgg ccacgggttt 180
acacacgcgc acatcgttgc gttaagccaa cacccggcag cgttagggac cgtcgctgtc 240
aagtatcagg acatgatcgc agcgttgcca gaggcgacac acgaagcgat cgttggcgtc 300
ggcaaacagt ggtccggcgc acgcgctctg gaggccttgc tcacggtggc gggagagttg 360
agaggtccac cgttacagtt ggacacaggc caacttctca agattgcaaa acgtggcggc 420
gtgaccgcag tggaggcagt gcatgcatgg cgcaatgcac tgacgggtgc cccgctcaac 480
ttgacccccc agcaggtggt ggccatcgcc agcaataatg gtggcaagca ggcgctggag 540
acggtccagc ggctgttgcc ggtgctgtgc caggcccacg gcttgacccc ccagcaggtg 600
gtggccatcg ccagcaatgg cggtggcaag caggcgctgg agacggtcca gcggctgttg 660
ccggtgctgt gccaggccca cggcttgacc ccccagcagg tggtggccat cgccagcaat 720
ggcggtggca agcaggcgct ggagacggtc cagcggctgt tgccggtgct gtgccaggcc 780
cacggcttga ccccggagca ggtggtggcc atcgccagcc acgatggcgg caagcaggcg 840
ctggagacgg tccagcggct gttgccggtg ctgtgccagg cccacggctt gaccccccag 900
caggtggtgg ccatcgccag caatggcggt ggcaagcagg cgctggagac ggtccagcgg 960
ctgttgccgg tgctgtgcca ggcccacggc ttgacccccc agcaggtggt ggccatcgcc 1020
agcaatggcg gtggcaagca ggcgctggag acggtccagc ggctgttgcc ggtgctgtgc 1080
caggcccacg gcttgacccc ccagcaggtg gtggccatcg ccagcaatgg cggtggcaag 1140
caggcgctgg agacggtcca gcggctgttg ccggtgctgt gccaggccca cggcttgacc 1200
ccccagcagg tggtggccat cgccagcaat ggcggtggca agcaggcgct ggagacggtc 1260
cagcggctgt tgccggtgct gtgccaggcc cacggcttga ccccccagca ggtggtggcc 1320
atcgccagca ataatggtgg caagcaggcg ctggagacgg tccagcggct gttgccggtg 1380
ctgtgccagg cccacggctt gaccccccag caggtggtgg ccatcgccag caataatggt 1440
ggcaagcagg cgctggagac ggtccagcgg ctgttgccgg tgctgtgcca ggcccacggc 1500
ttgacccccc agcaggtggt ggccatcgcc agcaatggcg gtggcaagca ggcgctggag 1560
acggtccagc ggctgttgcc ggtgctgtgc caggcccacg gcttgacccc ccagcaggtg 1620
gtggccatcg ccagcaatgg cggtggcaag caggcgctgg agacggtcca gcggctgttg 1680
ccggtgctgt gccaggccca cggcttgacc ccccagcagg tggtggccat cgccagcaat 1740
ggcggtggca agcaggcgct ggagacggtc cagcggctgt tgccggtgct gtgccaggcc 1800
cacggcttga ccccccagca ggtggtggcc atcgccagca atggcggtgg caagcaggcg 1860
ctggagacgg tccagcggct gttgccggtg ctgtgccagg cccacggctt gaccccggag 1920
caggtggtgg ccatcgccag ccacgatggc ggcaagcagg cgctggagac ggtccagcgg 1980
ctgttgccgg tgctgtgcca ggcccacggc ttgacccctc agcaggtggt ggccatcgcc 2040
agcaatggcg gcggcaggcc ggcgctggag agcattgttg cccagttatc tcgccctgat 2100
ccgagtggca gcggaagtgg cggggatcct atcagccgtt cccagctggt gaagtccgag 2160
ctggaggaga agaaatccga gttgaggcac aagctgaagt acgtgcccca cgagtacatc 2220
gagctgatcg agatcgcccg gaacagcacc caggaccgta tcctggagat gaaggtgatg 2280
gagttcttca tgaaggtgta cggctacagg ggcaagcacc tgggcggctc caggaagccc 2340
gacggcgcca tctacaccgt gggctccccc atcgactacg gcgtgatcgt ggacaccaag 2400
gcctactccg gcggctacaa cctgcccatc ggccaggccg acgaaatgca gaggtacgtg 2460
gaggagaacc agaccaggaa caagcacatc aaccccaacg agtggtggaa ggtgtacccc 2520
tccagcgtga ccgagttcaa gttcctgttc gtgtccggcc acttcaaggg caactacaag 2580
gcccagctga ccaggctgaa ccacatcacc aactgcaacg gcgccgtgct gtccgtggag 2640
gagctcctga tcggcggcga gatgatcaag gccggcaccc tgaccctgga ggaggtgagg 2700
aggaagttca acaacggcga gatcaacttc gcggccgact gataa 2745
<210> 25
<211> 2745
<212> DNA
<213> artificial sequence
<220>
<223> TALEN CD25 pCLS30479
<400> 25
atgggcgatc ctaaaaagaa acgtaaggtc atcgattacc catacgatgt tccagattac 60
gctatcgata tcgccgatct acgcacgctc ggctacagcc agcagcaaca ggagaagatc 120
aaaccgaagg ttcgttcgac agtggcgcag caccacgagg cactggtcgg ccacgggttt 180
acacacgcgc acatcgttgc gttaagccaa cacccggcag cgttagggac cgtcgctgtc 240
aagtatcagg acatgatcgc agcgttgcca gaggcgacac acgaagcgat cgttggcgtc 300
ggcaaacagt ggtccggcgc acgcgctctg gaggccttgc tcacggtggc gggagagttg 360
agaggtccac cgttacagtt ggacacaggc caacttctca agattgcaaa acgtggcggc 420
gtgaccgcag tggaggcagt gcatgcatgg cgcaatgcac tgacgggtgc cccgctcaac 480
ttgaccccgg agcaggtggt ggccatcgcc agcaatattg gtggcaagca ggcgctggag 540
acggtgcagg cgctgttgcc ggtgctgtgc caggcccacg gcttgacccc ggagcaggtg 600
gtggccatcg ccagccacga tggcggcaag caggcgctgg agacggtcca gcggctgttg 660
ccggtgctgt gccaggccca cggcttgacc ccggagcagg tggtggccat cgccagcaat 720
attggtggca agcaggcgct ggagacggtg caggcgctgt tgccggtgct gtgccaggcc 780
cacggcttga ccccccagca ggtggtggcc atcgccagca ataatggtgg caagcaggcg 840
ctggagacgg tccagcggct gttgccggtg ctgtgccagg cccacggctt gaccccccag 900
caggtggtgg ccatcgccag caataatggt ggcaagcagg cgctggagac ggtccagcgg 960
ctgttgccgg tgctgtgcca ggcccacggc ttgaccccgg agcaggtggt ggccatcgcc 1020
agcaatattg gtggcaagca ggcgctggag acggtgcagg cgctgttgcc ggtgctgtgc 1080
caggcccacg gcttgacccc ccagcaggtg gtggccatcg ccagcaataa tggtggcaag 1140
caggcgctgg agacggtcca gcggctgttg ccggtgctgt gccaggccca cggcttgacc 1200
ccccagcagg tggtggccat cgccagcaat aatggtggca agcaggcgct ggagacggtc 1260
cagcggctgt tgccggtgct gtgccaggcc cacggcttga ccccggagca ggtggtggcc 1320
atcgccagca atattggtgg caagcaggcg ctggagacgg tgcaggcgct gttgccggtg 1380
ctgtgccagg cccacggctt gaccccggag caggtggtgg ccatcgccag caatattggt 1440
ggcaagcagg cgctggagac ggtgcaggcg ctgttgccgg tgctgtgcca ggcccacggc 1500
ttgacccccc agcaggtggt ggccatcgcc agcaataatg gtggcaagca ggcgctggag 1560
acggtccagc ggctgttgcc ggtgctgtgc caggcccacg gcttgacccc ggagcaggtg 1620
gtggccatcg ccagcaatat tggtggcaag caggcgctgg agacggtgca ggcgctgttg 1680
ccggtgctgt gccaggccca cggcttgacc ccccagcagg tggtggccat cgccagcaat 1740
aatggtggca agcaggcgct ggagacggtc cagcggctgt tgccggtgct gtgccaggcc 1800
cacggcttga ccccccagca ggtggtggcc atcgccagca atggcggtgg caagcaggcg 1860
ctggagacgg tccagcggct gttgccggtg ctgtgccagg cccacggctt gaccccggag 1920
caggtggtgg ccatcgccag caatattggt ggcaagcagg cgctggagac ggtgcaggcg 1980
ctgttgccgg tgctgtgcca ggcccacggc ttgacccctc agcaggtggt ggccatcgcc 2040
agcaatggcg gcggcaggcc ggcgctggag agcattgttg cccagttatc tcgccctgat 2100
ccgagtggca gcggaagtgg cggggatcct atcagccgtt cccagctggt gaagtccgag 2160
ctggaggaga agaaatccga gttgaggcac aagctgaagt acgtgcccca cgagtacatc 2220
gagctgatcg agatcgcccg gaacagcacc caggaccgta tcctggagat gaaggtgatg 2280
gagttcttca tgaaggtgta cggctacagg ggcaagcacc tgggcggctc caggaagccc 2340
gacggcgcca tctacaccgt gggctccccc atcgactacg gcgtgatcgt ggacaccaag 2400
gcctactccg gcggctacaa cctgcccatc ggccaggccg acgaaatgca gaggtacgtg 2460
gaggagaacc agaccaggaa caagcacatc aaccccaacg agtggtggaa ggtgtacccc 2520
tccagcgtga ccgagttcaa gttcctgttc gtgtccggcc acttcaaggg caactacaag 2580
gcccagctga ccaggctgaa ccacatcacc aactgcaacg gcgccgtgct gtccgtggag 2640
gagctcctga tcggcggcga gatgatcaag gccggcaccc tgaccctgga ggaggtgagg 2700
aggaagttca acaacggcga gatcaacttc gcggccgact gataa 2745
<210> 26
<211> 2814
<212> DNA
<213> artificial sequence
<220>
<223> TALEN PD1 pCLS28959
<400> 26
atgggcgatc ctaaaaagaa acgtaaggtc atcgattacc catacgatgt tccagattac 60
gctatcgata tcgccgatct acgcacgctc ggctacagcc agcagcaaca ggagaagatc 120
aaaccgaagg ttcgttcgac agtggcgcag caccacgagg cactggtcgg ccacgggttt 180
acacacgcgc acatcgttgc gttaagccaa cacccggcag cgttagggac cgtcgctgtc 240
aagtatcagg acatgatcgc agcgttgcca gaggcgacac acgaagcgat cgttggcgtc 300
ggcaaacagt ggtccggcgc acgcgctctg gaggccttgc tcacggtggc gggagagttg 360
agaggtccac cgttacagtt ggacacaggc caacttctca agattgcaaa acgtggcggc 420
gtgaccgcag tggaggcagt gcatgcatgg cgcaatgcac tgacgggtgc cccgctcaac 480
ttgacccccg agcaagtggt ggctatcgct tccaagctgg ggggaaagca ggccctggag 540
accgtccagg cccttctccc agtgctttgc caggctcacg gactgacccc tgaacaggtg 600
gtggcaattg cctcacacga cgggggcaag caggcactgg agactgtcca gcggctgctg 660
cctgtcctct gccaggccca cggactcact cctgagcagg tcgtggccat tgccagccac 720
gatgggggca aacaggctct ggagaccgtg cagcgcctcc tcccagtgct gtgccaggct 780
catgggctga ccccacagca ggtcgtcgcc attgccagta acggcggggg gaagcaggcc 840
ctcgaaacag tgcagaggct gctgcccgtc ttgtgccaag cacacggcct gacacccgag 900
caggtggtgg ccatcgcctc tcatgacggc ggcaagcagg cccttgagac agtgcagaga 960
ctgttgcccg tgttgtgtca ggcccacggg ttgacacccc agcaggtggt cgccatcgcc 1020
agcaatggcg ggggaaagca ggcccttgag accgtgcagc ggttgcttcc agtgttgtgc 1080
caggcacacg gactgacccc tcaacaggtg gtcgcaatcg ccagctacaa gggcggaaag 1140
caggctctgg agacagtgca gcgcctcctg cccgtgctgt gtcaggctca cggactgaca 1200
ccacagcagg tggtcgccat cgccagtaac gggggcggca agcaggcttt ggagaccgtc 1260
cagagactcc tccccgtcct ttgccaggcc cacgggttga cacctcagca ggtcgtcgcc 1320
attgcctcca acaacggggg caagcaggcc ctcgaaactg tgcagaggct gctgcctgtg 1380
ctgtgccagg ctcatgggct gacaccccag caggtggtgg ccattgcctc taacaacggc 1440
ggcaaacagg cactggagac cgtgcaaagg ctgctgcccg tcctctgcca agcccacggg 1500
ctcactccac agcaggtcgt ggccatcgcc tcaaacaatg gcgggaagca ggccctggag 1560
actgtgcaaa ggctgctccc tgtgctctgc caggcacacg gactgacccc tcagcaggtg 1620
gtggcaatcg cttccaacaa cgggggaaag caggccctcg aaaccgtgca gcgcctcctc 1680
ccagtgctgt gccaggcaca tggcctcaca cccgagcaag tggtggctat cgccagccac 1740
gacggaggga agcaggctct ggagaccgtg cagaggctgc tgcctgtcct gtgccaggcc 1800
cacgggctta ctccagagca ggtcgtcgcc atcgccagtc atgatggggg gaagcaggcc 1860
cttgagacag tccagcggct gctgccagtc ctttgccagg ctcacggctt gactcccgag 1920
caggtcgtgg ccattgcctc aaacattggg ggcaaacagg ccctggagac agtgcaggcc 1980
ctgctgcccg tgttgtgtca ggcccacggc ttgacacccc agcaggtggt cgccattgcc 2040
tctaatggcg gcgggagacc cgccttggag agcattgttg cccagttatc tcgccctgat 2100
ccggcgttgg ccgcgttgac caacgaccac ctcgtcgcct tggcctgcct cggcgggcgt 2160
cctgcgctgg atgcagtgaa aaagggattg ggggatccta tcagccgttc ccagctggtg 2220
aagtccgagc tggaggagaa gaaatccgag ttgaggcaca agctgaagta cgtgccccac 2280
gagtacatcg agctgatcga gatcgcccgg aacagcaccc aggaccgtat cctggagatg 2340
aaggtgatgg agttcttcat gaaggtgtac ggctacaggg gcaagcacct gggcggctcc 2400
aggaagcccg acggcgccat ctacaccgtg ggctccccca tcgactacgg cgtgatcgtg 2460
gacaccaagg cctactccgg cggctacaac ctgcccatcg gccaggccga cgaaatgcag 2520
aggtacgtgg aggagaacca gaccaggaac aagcacatca accccaacga gtggtggaag 2580
gtgtacccct ccagcgtgac cgagttcaag ttcctgttcg tgtccggcca cttcaagggc 2640
aactacaagg cccagctgac caggctgaac cacatcacca actgcaacgg cgccgtgctg 2700
tccgtggagg agctcctgat cggcggcgag atgatcaagg ccggcaccct gaccctggag 2760
gaggtgagga ggaagttcaa caacggcgag atcaacttcg cggccgactg ataa 2814
<210> 27
<211> 2829
<212> DNA
<213> artificial sequence
<220>
<223> TALEN PD1 pCLS18792
<400> 27
atgggcgatc ctaaaaagaa acgtaaggtc atcgataagg agaccgccgc tgccaagttc 60
gagagacagc acatggacag catcgatatc gccgatctac gcacgctcgg ctacagccag 120
cagcaacagg agaagatcaa accgaaggtt cgttcgacag tggcgcagca ccacgaggca 180
ctggtcggcc acgggtttac acacgcgcac atcgttgcgt taagccaaca cccggcagcg 240
ttagggaccg tcgctgtcaa gtatcaggac atgatcgcag cgttgccaga ggcgacacac 300
gaagcgatcg ttggcgtcgg caaacagtgg tccggcgcac gcgctctgga ggccttgctc 360
acggtggcgg gagagttgag aggtccaccg ttacagttgg acacaggcca acttctcaag 420
attgcaaaac gtggcggcgt gaccgcagtg gaggcagtgc atgcatggcg caatgcactg 480
acgggtgccc cgctcaactt gacccccgag caagtcgtcg caatcgccag ccatgatgga 540
gggaagcaag ccctcgaaac cgtgcagcgg ttgcttcctg tgctctgcca ggcccacggc 600
cttacccctc agcaggtggt ggccatcgca agtaacggag gaggaaagca agccttggag 660
acagtgcagc gcctgttgcc cgtgctgtgc caggcacacg gcctcacacc agagcaggtc 720
gtggccattg cctcccatga cggggggaaa caggctctgg agaccgtcca gaggctgctg 780
cccgtcctct gtcaagctca cggcctgact ccccaacaag tggtcgccat cgcctctaat 840
ggcggcggga agcaggcact ggaaacagtg cagagactgc tccctgtgct ttgccaagct 900
catgggttga ccccccaaca ggtcgtcgct attgcctcaa acgggggggg caagcaggcc 960
cttgagactg tgcagaggct gttgccagtg ctgtgtcagg ctcacgggct cactccacaa 1020
caggtggtcg caattgccag caacggcggc ggaaagcaag ctcttgaaac cgtgcaacgc 1080
ctcctgcccg tgctctgtca ggctcatggc ctgacaccac aacaagtcgt ggccatcgcc 1140
agtaataatg gcgggaaaca ggctcttgag accgtccaga ggctgctccc agtgctctgc 1200
caggcacacg ggctgacccc cgagcaggtg gtggctatcg ccagcaatat tgggggcaag 1260
caggccctgg aaacagtcca ggccctgctg ccagtgcttt gccaggctca cgggctcact 1320
ccccagcagg tcgtggcaat cgcctccaac ggcggaggga agcaggctct ggagaccgtg 1380
cagagactgc tgcccgtctt gtgccaggcc cacggactca cacctgaaca ggtcgtcgcc 1440
attgcctctc acgatggggg caaacaagcc ctggagacag tgcagcggct gttgcctgtg 1500
ttgtgccaag cccacggctt gactcctcaa caagtggtcg ccatcgcctc aaatggcggc 1560
ggaaaacaag ctctggagac agtgcagagg ttgctgcccg tcctctgcca agcccacggc 1620
ctgactcccc aacaggtcgt cgccattgcc agcaacaacg gaggaaagca ggctctcgaa 1680
actgtgcagc ggctgcttcc tgtgctgtgt caggctcatg ggctgacccc cgagcaagtg 1740
gtggctattg cctctaatgg aggcaagcaa gcccttgaga cagtccagag gctgttgcca 1800
gtgctgtgcc aggcccacgg gctcacaccc cagcaggtgg tcgccatcgc cagtaacaac 1860
gggggcaaac aggcattgga aaccgtccag cgcctgcttc cagtgctctg ccaggcacac 1920
ggactgacac ccgaacaggt ggtggccatt gcatcccatg atgggggcaa gcaggccctg 1980
gagaccgtgc agagactcct gccagtgttg tgccaagctc acggcctcac ccctcagcaa 2040
gtcgtggcca tcgcctcaaa cggggggggc cggcctgcac tggagagcat tgttgcccag 2100
ttatctcgcc ctgatccggc gttggccgcg ttgaccaacg accacctcgt cgccttggcc 2160
tgcctcggcg ggcgtcctgc gctggatgca gtgaaaaagg gattggggga tcctatcagc 2220
cgttcccagc tggtgaagtc cgagctggag gagaagaaat ccgagttgag gcacaagctg 2280
aagtacgtgc cccacgagta catcgagctg atcgagatcg cccggaacag cacccaggac 2340
cgtatcctgg agatgaaggt gatggagttc ttcatgaagg tgtacggcta caggggcaag 2400
cacctgggcg gctccaggaa gcccgacggc gccatctaca ccgtgggctc ccccatcgac 2460
tacggcgtga tcgtggacac caaggcctac tccggcggct acaacctgcc catcggccag 2520
gccgacgaaa tgcagaggta cgtggaggag aaccagacca ggaacaagca catcaacccc 2580
aacgagtggt ggaaggtgta cccctccagc gtgaccgagt tcaagttcct gttcgtgtcc 2640
ggccacttca agggcaacta caaggcccag ctgaccaggc tgaaccacat caccaactgc 2700
aacggcgccg tgctgtccgt ggaggagctc ctgatcggcg gcgagatgat caaggccggc 2760
accctgaccc tggaggaggt gaggaggaag ttcaacaacg gcgagatcaa cttcgcggcc 2820
gactgataa 2829
<210> 28
<211> 49
<212> DNA
<213> artificial sequence
<220>
<223> TALEN target TRAC
<400> 28
ttgtcccaca gatatccaga accctgaccc tgccgtgtac cagctgaga 49
<210> 29
<211> 45
<212> DNA
<213> artificial sequence
<220>
<223> TALEN target CD25
<400> 29
tacaggagga agagtagaag aacaatctag aaaaccaaaa gaaca 45
<210> 30
<211> 49
<212> DNA
<213> artificial sequence
<220>
<223> TALEN target PD1
<400> 30
tacctctgtg gggccatctc cctggccccc aaggcgcaga tcaaagaga 49
<210> 31
<211> 2897
<212> DNA
<213> artificial sequence
<220>
<223> Matrice TRAC locus_CubiCAR CD22 pCLS30056
<400> 31
ttgctgggcc tttttcccat gcctgccttt actctgccag agttatattg ctggggtttt 60
gaagaagatc ctattaaata aaagaataag cagtattatt aagtagccct gcatttcagg 120
tttccttgag tggcaggcca ggcctggccg tgaacgttca ctgaaatcat ggcctcttgg 180
ccaagattga tagcttgtgc ctgtccctga gtcccagtcc atcacgagca gctggtttct 240
aagatgctat ttcccgtata aagcatgaga ccgtgacttg ccagccccac agagccccgc 300
ccttgtccat cactggcatc tggactccag cctgggttgg ggcaaagagg gaaatgagat 360
catgtcctaa ccctgatcct cttgtcccac agatatccag tacccctacg acgtgcccga 420
ctacgcctcc ggtgagggca gaggaagtct tctaacatgc ggtgacgtgg aggagaatcc 480
gggccccgga tccgctctgc ccgtcaccgc tctgctgctg ccactggcac tgctgctgca 540
cgctgctagg cccggagggg gaggcagctg cccctacagc aaccccagcc tgtgcagcgg 600
aggcggcggc agcggcggag ggggtagcca ggtgcagctg cagcagagcg gccctggcct 660
ggtgaagcca agccagacac tgtccctgac ctgcgccatc agcggcgatt ccgtgagctc 720
caactccgcc gcctggaatt ggatcaggca gtccccttct cggggcctgg agtggctggg 780
aaggacatac tatcggtcta agtggtacaa cgattatgcc gtgtctgtga agagcagaat 840
cacaatcaac cctgacacct ccaagaatca gttctctctg cagctgaata gcgtgacacc 900
agaggacacc gccgtgtact attgcgccag ggaggtgacc ggcgacctgg aggatgcctt 960
tgacatctgg ggccagggca caatggtgac cgtgagctcc ggaggcggcg gatctggcgg 1020
aggaggaagt gggggcggcg ggagtgatat ccagatgaca cagtccccat cctctctgag 1080
cgcctccgtg ggcgacagag tgacaatcac ctgtagggcc tcccagacca tctggtctta 1140
cctgaactgg tatcagcaga ggcccggcaa ggcccctaat ctgctgatct acgcagcaag 1200
ctccctgcag agcggagtgc catccagatt ctctggcagg ggctccggca cagacttcac 1260
cctgaccatc tctagcctgc aggccgagga cttcgccacc tactattgcc agcagtctta 1320
tagcatcccc cagacatttg gccagggcac caagctggag atcaagtcgg atcccggaag 1380
cggaggggga ggcagctgcc cctacagcaa ccccagcctg tgcagcggag gcggcggcag 1440
cgagctgccc acccagggca ccttctccaa cgtgtccacc aacgtgagcc cagccaagcc 1500
caccaccacc gcctgtcctt attccaatcc ttccctgtgt gctcccacca caacccccgc 1560
tccaaggccc cctacccccg caccaactat tgcctcccag ccactctcac tgcggcctga 1620
ggcctgtcgg cccgctgctg gaggcgcagt gcatacaagg ggcctcgatt tcgcctgcga 1680
tatttacatc tgggcacccc tcgccggcac ctgcggggtg cttctcctct ccctggtgat 1740
taccctgtat tgcagacggg gccggaagaa gctcctctac atttttaagc agcctttcat 1800
gcggccagtg cagacaaccc aagaggagga tgggtgttcc tgcagattcc ctgaggaaga 1860
ggaaggcggg tgcgagctga gagtgaagtt ctccaggagc gcagatgccc ccgcctatca 1920
acagggccag aaccagctct acaacgagct taacctcggg aggcgcgaag aatacgacgt 1980
gttggataag agaagggggc gggaccccga gatgggagga aagccccgga ggaagaaccc 2040
tcaggagggc ctgtacaacg agctgcagaa ggataagatg gccgaggcct actcagagat 2100
cgggatgaag ggggagcggc gccgcgggaa ggggcacgat gggctctacc aggggctgag 2160
cacagccaca aaggacacat acgacgcctt gcacatgcag gcccttccac cccgggaata 2220
gtctagaggg cccgtttaaa cccgctgatc agcctcgact gtgccttcta gttgccagcc 2280
atctgttgtt tgcccctccc ccgtgccttc cttgaccctg gaaggtgcca ctcccactgt 2340
cctttcctaa taaaatgagg aaattgcatc gcattgtctg agtaggtgtc attctattct 2400
ggggggtggg gtggggcagg acagcaaggg ggaggattgg gaagacaata gcaggcatgc 2460
tggggatgcg gtgggctcta tgactagtgg cgaattcccg tgtaccagct gagagactct 2520
aaatccagtg acaagtctgt ctgcctattc accgattttg attctcaaac aaatgtgtca 2580
caaagtaagg attctgatgt gtatatcaca gacaaaactg tgctagacat gaggtctatg 2640
gacttcaaga gcaacagtgc tgtggcctgg agcaacaaat ctgactttgc atgtgcaaac 2700
gccttcaaca acagcattat tccagaagac accttcttcc ccagcccagg taagggcagc 2760
tttggtgcct tcgcaggctg tttccttgct tcaggaatgg ccaggttctg cccagagctc 2820
tggtcaatga tgtctaaaac tcctctgatt ggtggtctcg gccttatcca ttgccaccaa 2880
aaccctcttt ttactaa 2897
<210> 32
<211> 2688
<212> DNA
<213> artificial sequence
<220>
<223> Matrice CD25 locus_IL15_2A_sIL15Ra pCLS30519
<400> 32
gtttattatt cctgttccac agctattgtc tgccatataa aaacttaggc caggcacagt 60
ggctcacacc tgtaatccca gcactttgga aggccgaggc aggcagatca caaggtcagg 120
agttcgagac cagcctggcc aacatagcaa aaccccatct ctactaaaaa tacaaaaatt 180
agccaggcat ggtggcgtgt gcactggttt agagtgagga ccacattttt ttggtgccgt 240
gttacacata tgaccgtgac tttgttacac cactacagga ggaagagtag aagaacaatc 300
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 360
tccaacccag ggcccggtac cgggtccgcc accatggact ggacctggat tctgttcctc 420
gtggctgctg ctacaagagt gcacagcggc attcatgtct tcattttggg ctgtttcagt 480
gcagggcttc ctaaaacaga agccaactgg gtgaatgtaa taagtgattt gaaaaaaatt 540
gaagatctta ttcaatctat gcatattgat gctactttat atacggaaag tgatgttcac 600
cccagttgca aagtaacagc aatgaagtgc tttctcttgg agttacaagt tatttcactt 660
gagtccggag atgcaagtat tcatgataca gtagaaaatc tgatcatcct agcaaacaac 720
agtttgtctt ctaatgggaa tgtaacagaa tctggatgca aagaatgtga ggaactggag 780
gaaaaaaata ttaaagaatt tttgcagagt tttgtacata ttgtccaaat gttcatcaac 840
acttctggaa gcggagctac taacttcagc ctgctgaagc aggctggaga cgtggaggag 900
aaccctggac ctgggaccgg ctctgcaacc atggattgga cgtggatcct gtttctcgtg 960
gcagctgcca caagagttca cagtatcacg tgccctcccc ccatgtccgt ggaacacgca 1020
gacatctggg tcaagagcta cagcttgtac tccagggagc ggtacatttg taactctggt 1080
ttcaagcgta aagccggcac gtccagcctg acggagtgcg tgttgaacaa ggccacgaat 1140
gtcgcccact ggacaacccc cagtctcaaa tgcattagag accctgccct ggttcaccaa 1200
aggccagcgc caccctccac agtaacgacg gcaggggtga ccccacagcc agagagcctc 1260
tccccttctg gaaaagagcc cgcagcttca tctcccagct caaacaacac agcggccaca 1320
acagcagcta ttgtcccggg ctcccagctg atgccttcaa aatcaccttc cacaggaacc 1380
acagagataa gcagtcatga gtcctcccac ggcaccccct ctcagacaac agccaagaac 1440
tgggaactca cagcatccgc ctcccaccag ccgccaggtg tgtatccaca gggccacagc 1500
gacaccactg agggcagagg cagcctgctg acctgcggcg acgtcgagga gaaccccggg 1560
cccatggggg caggtgccac cggccgcgcc atggacgggc cgcgcctgct gctgttgctg 1620
cttctggggg tgtcccttgg aggtgccaag gaggcatgcc ccacaggcct gtacacacac 1680
agcggtgagt gctgcaaagc ctgcaacctg ggcgagggtg tggcccagcc ttgtggagcc 1740
aaccagaccg tgtgtgagcc ctgcctggac agcgtgacgt tctccgacgt ggtgagcgcg 1800
accgagccgt gcaagccgtg caccgagtgc gtggggctcc agagcatgtc ggcgccgtgc 1860
gtggaggccg atgacgccgt gtgccgctgc gcctacggct actaccagga tgagacgact 1920
gggcgctgcg aggcgtgccg cgtgtgcgag gcgggctcgg gcctcgtgtt ctcctgccag 1980
gacaagcaga acaccgtgtg cgaggagtgc cccgacggca cgtattccga cgaggccaac 2040
cacgtggacc cgtgcctgcc ctgcaccgtg tgcgaggaca ccgagcgcca gctccgcgag 2100
tgcacacgct gggccgacgc cgagtgcgag gagatccctg gccgttggat tacacggtcc 2160
acacccccag agggctcgga cagcacagcc cccagcaccc aggagcctga ggcacctcca 2220
gaacaagacc tcatagccag cacggtggca ggtgtggtga ccacagtgat gggcagctcc 2280
cagcccgtgg tgacccgagg caccaccgac aacctcatcc ctgtctattg ctccatcctg 2340
gctgctgtgg ttgtgggtct tgtggcctac atagccttca agaggtgaaa aaccaaaaga 2400
acaagaattt cttggtaaga agccgggaac agacaacaga agtcatgaag cccaagtgaa 2460
atcaaaggtg ctaaatggtc gcccaggaga catccgttgt gcttgcctgc gttttggaag 2520
ctctgaagtc acatcacagg acacggggca gtggcaacct tgtctctatg ccagctcagt 2580
cccatcagag agcgagcgct acccacttct aaatagcaat ttcgccgttg aagaggaagg 2640
gcaaaaccac tagaactctc catcttattt tcatgtatat gtgttcat 2688
<210> 33
<211> 2964
<212> DNA
<213> artificial sequence
<220>
<223> Matrice PD1 locus_IL15_2A_sIL15Ra pCLS30513
<400> 33
gactccccag acaggccctg gaaccccccc accttctccc cagccctgct cgtggtgacc 60
gaaggggaca acgccacctt cacctgcagc ttctccaaca catcggagag cttcgtgcta 120
aactggtacc gcatgagccc cagcaaccag acggacaagc tggccgcctt ccccgaggac 180
cgcagccagc ccggccagga ctgccgcttc cgtgtcacac aactgcccaa cgggcgtgac 240
ttccacatga gcgtggtcag ggcccggcgc aatgacagcg gcacctacct ctgtggggcc 300
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 360
tccaacccag ggcccggtac cgggtccgcc accatggact ggacctggat tctgttcctc 420
gtggctgctg ctacaagagt gcacagcggc attcatgtct tcattttggg ctgtttcagt 480
gcagggcttc ctaaaacaga agccaactgg gtgaatgtaa taagtgattt gaaaaaaatt 540
gaagatctta ttcaatctat gcatattgat gctactttat atacggaaag tgatgttcac 600
cccagttgca aagtaacagc aatgaagtgc tttctcttgg agttacaagt tatttcactt 660
gagtccggag atgcaagtat tcatgataca gtagaaaatc tgatcatcct agcaaacaac 720
agtttgtctt ctaatgggaa tgtaacagaa tctggatgca aagaatgtga ggaactggag 780
gaaaaaaata ttaaagaatt tttgcagagt tttgtacata ttgtccaaat gttcatcaac 840
acttctggaa gcggagctac taacttcagc ctgctgaagc aggctggaga cgtggaggag 900
aaccctggac ctgggaccgg ctctgcaacc atggattgga cgtggatcct gtttctcgtg 960
gcagctgcca caagagttca cagtatcacg tgccctcccc ccatgtccgt ggaacacgca 1020
gacatctggg tcaagagcta cagcttgtac tccagggagc ggtacatttg taactctggt 1080
ttcaagcgta aagccggcac gtccagcctg acggagtgcg tgttgaacaa ggccacgaat 1140
gtcgcccact ggacaacccc cagtctcaaa tgcattagag accctgccct ggttcaccaa 1200
aggccagcgc caccctccac agtaacgacg gcaggggtga ccccacagcc agagagcctc 1260
tccccttctg gaaaagagcc cgcagcttca tctcccagct caaacaacac agcggccaca 1320
acagcagcta ttgtcccggg ctcccagctg atgccttcaa aatcaccttc cacaggaacc 1380
acagagataa gcagtcatga gtcctcccac ggcaccccct ctcagacaac agccaagaac 1440
tgggaactca cagcatccgc ctcccaccag ccgccaggtg tgtatccaca gggccacagc 1500
gacaccactg agggcagagg cagcctgctg acctgcggcg acgtcgagga gaaccccggg 1560
cccatggggg caggtgccac cggccgcgcc atggacgggc cgcgcctgct gctgttgctg 1620
cttctggggg tgtcccttgg aggtgccaag gaggcatgcc ccacaggcct gtacacacac 1680
agcggtgagt gctgcaaagc ctgcaacctg ggcgagggtg tggcccagcc ttgtggagcc 1740
aaccagaccg tgtgtgagcc ctgcctggac agcgtgacgt tctccgacgt ggtgagcgcg 1800
accgagccgt gcaagccgtg caccgagtgc gtggggctcc agagcatgtc ggcgccgtgc 1860
gtggaggccg atgacgccgt gtgccgctgc gcctacggct actaccagga tgagacgact 1920
gggcgctgcg aggcgtgccg cgtgtgcgag gcgggctcgg gcctcgtgtt ctcctgccag 1980
gacaagcaga acaccgtgtg cgaggagtgc cccgacggca cgtattccga cgaggccaac 2040
cacgtggacc cgtgcctgcc ctgcaccgtg tgcgaggaca ccgagcgcca gctccgcgag 2100
tgcacacgct gggccgacgc cgagtgcgag gagatccctg gccgttggat tacacggtcc 2160
acacccccag agggctcgga cagcacagcc cccagcaccc aggagcctga ggcacctcca 2220
gaacaagacc tcatagccag cacggtggca ggtgtggtga ccacagtgat gggcagctcc 2280
cagcccgtgg tgacccgagg caccaccgac aacctcatcc ctgtctattg ctccatcctg 2340
gctgctgtgg ttgtgggtct tgtggcctac atagccttca agaggtgatc tagagggccc 2400
gtttaaaccc gctgatcagc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc 2460
ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa 2520
aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg 2580
gggcaggaca gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg 2640
ggctctatga ctagtggcga attcggcgca gatcaaagag agcctgcggg cagagctcag 2700
ggtgacaggt gcggcctcgg aggccccggg gcaggggtga gctgagccgg tcctggggtg 2760
ggtgtcccct cctgcacagg atcaggagct ccagggtcgt agggcaggga ccccccagct 2820
ccagtccagg gctctgtcct gcacctgggg aatggtgacc ggcatctctg tcctctagct 2880
ctggaagcac cccagcccct ctagtctgcc ctcacccctg accctgaccc tccaccctga 2940
ccccgtccta acccctgacc tttg 2964
<210> 34
<211> 3363
<212> DNA
<213> artificial sequence
<220>
<223> Matrice CD25 locus_IL12a_2A_IL12b pCLS30520
<400> 34
gtttattatt cctgttccac agctattgtc tgccatataa aaacttaggc caggcacagt 60
ggctcacacc tgtaatccca gcactttgga aggccgaggc aggcagatca caaggtcagg 120
agttcgagac cagcctggcc aacatagcaa aaccccatct ctactaaaaa tacaaaaatt 180
agccaggcat ggtggcgtgt gcactggttt agagtgagga ccacattttt ttggtgccgt 240
gttacacata tgaccgtgac tttgttacac cactacagga ggaagagtag aagaacaatc 300
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 360
tccaacccag ggcccatgtg gccccctggg tcagcctccc agccaccgcc ctcacctgcc 420
gcggccacag gtctgcatcc agcggctcgc cctgtgtccc tgcagtgccg gctcagcatg 480
tgtccagcgc gcagcctcct ccttgtggct accctggtcc tcctggacca cctcagtttg 540
gccagaaacc tccccgtggc cactccagac ccaggaatgt tcccatgcct tcaccactcc 600
caaaacctgc tgagggccgt cagcaacatg ctccagaagg ccagacaaac tctagaattt 660
tacccttgca cttctgaaga gattgatcat gaagatatca caaaagataa aaccagcaca 720
gtggaggcct gtttaccatt ggaattaacc aagaatgaga gttgcctaaa ttccagagag 780
acctctttca taactaatgg gagttgcctg gcctccagaa agacctcttt tatgatggcc 840
ctgtgcctta gtagtattta tgaagacttg aagatgtacc aggtggagtt caagaccatg 900
aatgcaaagc ttctgatgga tcctaagagg cagatctttc tagatcaaaa catgctggca 960
gttattgatg agctgatgca ggccctgaat ttcaacagtg agactgtgcc acaaaaatcc 1020
tcccttgaag aaccggattt ttataaaact aaaatcaagc tctgcatact tcttcatgct 1080
ttcagaattc gggcagtgac tattgataga gtgatgagct atctgaatgc ttccggaagc 1140
ggagctacta acttcagcct gctgaagcag gctggagacg tggaggagaa ccctggacct 1200
atgtgtcacc agcagttggt catctcttgg ttttccctgg tttttctggc atctcccctc 1260
gtggccatat gggaactgaa gaaagatgtt tatgtcgtag aattggattg gtatccggat 1320
gcccctggag aaatggtggt cctcacctgt gacacccctg aagaagatgg tatcacctgg 1380
accttggacc agagcagtga ggtcttaggc tctggcaaaa ccctgaccat ccaagtcaaa 1440
gagtttggag atgctggcca gtacacctgt cacaaaggag gcgaggttct aagccattcg 1500
ctcctgctgc ttcacaaaaa ggaagatgga atttggtcca ctgatatttt aaaggaccag 1560
aaagaaccca aaaataagac ctttctaaga tgcgaggcca agaattattc tggacgtttc 1620
acctgctggt ggctgacgac aatcagtact gatttgacat tcagtgtcaa aagcagcaga 1680
ggctcttctg acccccaagg ggtgacgtgc ggagctgcta cactctctgc agagagagtc 1740
agaggggaca acaaggagta tgagtactca gtggagtgcc aggaggacag tgcctgccca 1800
gctgctgagg agagtctgcc cattgaggtc atggtggatg ccgttcacaa gctcaagtat 1860
gaaaactaca ccagcagctt cttcatcagg gacatcatca aacctgaccc acccaagaac 1920
ttgcagctga agccattaaa gaattctcgg caggtggagg tcagctggga gtaccctgac 1980
acctggagta ctccacattc ctacttctcc ctgacattct gcgttcaggt ccagggcaag 2040
agcaagagag aaaagaaaga tagagtcttc acggacaaga cctcagccac ggtcatctgc 2100
cgcaaaaatg ccagcattag cgtgcgggcc caggaccgct actatagctc atcttggagc 2160
gaatgggcat ctgtgccctg cagtgagggc agaggcagcc tgctgacctg cggcgacgtc 2220
gaggagaacc ccgggcccat gggggcaggt gccaccggcc gcgccatgga cgggccgcgc 2280
ctgctgctgt tgctgcttct gggggtgtcc cttggaggtg ccaaggaggc atgccccaca 2340
ggcctgtaca cacacagcgg tgagtgctgc aaagcctgca acctgggcga gggtgtggcc 2400
cagccttgtg gagccaacca gaccgtgtgt gagccctgcc tggacagcgt gacgttctcc 2460
gacgtggtga gcgcgaccga gccgtgcaag ccgtgcaccg agtgcgtggg gctccagagc 2520
atgtcggcgc cgtgcgtgga ggccgatgac gccgtgtgcc gctgcgccta cggctactac 2580
caggatgaga cgactgggcg ctgcgaggcg tgccgcgtgt gcgaggcggg ctcgggcctc 2640
gtgttctcct gccaggacaa gcagaacacc gtgtgcgagg agtgccccga cggcacgtat 2700
tccgacgagg ccaaccacgt ggacccgtgc ctgccctgca ccgtgtgcga ggacaccgag 2760
cgccagctcc gcgagtgcac acgctgggcc gacgccgagt gcgaggagat ccctggccgt 2820
tggattacac ggtccacacc cccagagggc tcggacagca cagcccccag cacccaggag 2880
cctgaggcac ctccagaaca agacctcata gccagcacgg tggcaggtgt ggtgaccaca 2940
gtgatgggca gctcccagcc cgtggtgacc cgaggcacca ccgacaacct catccctgtc 3000
tattgctcca tcctggctgc tgtggttgtg ggtcttgtgg cctacatagc cttcaagagg 3060
tgaaaaacca aaagaacaag aatttcttgg taagaagccg ggaacagaca acagaagtca 3120
tgaagcccaa gtgaaatcaa aggtgctaaa tggtcgccca ggagacatcc gttgtgcttg 3180
cctgcgtttt ggaagctctg aagtcacatc acaggacacg gggcagtggc aaccttgtct 3240
ctatgccagc tcagtcccat cagagagcga gcgctaccca cttctaaata gcaatttcgc 3300
cgttgaagag gaagggcaaa accactagaa ctctccatct tattttcatg tatatgtgtt 3360
cat 3363
<210> 35
<211> 3639
<212> DNA
<213> artificial sequence
<220>
<223> Matrice PD1 locus_IL12a_2A_IL12b pCLS30511
<400> 35
gactccccag acaggccctg gaaccccccc accttctccc cagccctgct cgtggtgacc 60
gaaggggaca acgccacctt cacctgcagc ttctccaaca catcggagag cttcgtgcta 120
aactggtacc gcatgagccc cagcaaccag acggacaagc tggccgcctt ccccgaggac 180
cgcagccagc ccggccagga ctgccgcttc cgtgtcacac aactgcccaa cgggcgtgac 240
ttccacatga gcgtggtcag ggcccggcgc aatgacagcg gcacctacct ctgtggggcc 300
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 360
tccaacccag ggcccatgtg gccccctggg tcagcctccc agccaccgcc ctcacctgcc 420
gcggccacag gtctgcatcc agcggctcgc cctgtgtccc tgcagtgccg gctcagcatg 480
tgtccagcgc gcagcctcct ccttgtggct accctggtcc tcctggacca cctcagtttg 540
gccagaaacc tccccgtggc cactccagac ccaggaatgt tcccatgcct tcaccactcc 600
caaaacctgc tgagggccgt cagcaacatg ctccagaagg ccagacaaac tctagaattt 660
tacccttgca cttctgaaga gattgatcat gaagatatca caaaagataa aaccagcaca 720
gtggaggcct gtttaccatt ggaattaacc aagaatgaga gttgcctaaa ttccagagag 780
acctctttca taactaatgg gagttgcctg gcctccagaa agacctcttt tatgatggcc 840
ctgtgcctta gtagtattta tgaagacttg aagatgtacc aggtggagtt caagaccatg 900
aatgcaaagc ttctgatgga tcctaagagg cagatctttc tagatcaaaa catgctggca 960
gttattgatg agctgatgca ggccctgaat ttcaacagtg agactgtgcc acaaaaatcc 1020
tcccttgaag aaccggattt ttataaaact aaaatcaagc tctgcatact tcttcatgct 1080
ttcagaattc gggcagtgac tattgataga gtgatgagct atctgaatgc ttccggaagc 1140
ggagctacta acttcagcct gctgaagcag gctggagacg tggaggagaa ccctggacct 1200
atgtgtcacc agcagttggt catctcttgg ttttccctgg tttttctggc atctcccctc 1260
gtggccatat gggaactgaa gaaagatgtt tatgtcgtag aattggattg gtatccggat 1320
gcccctggag aaatggtggt cctcacctgt gacacccctg aagaagatgg tatcacctgg 1380
accttggacc agagcagtga ggtcttaggc tctggcaaaa ccctgaccat ccaagtcaaa 1440
gagtttggag atgctggcca gtacacctgt cacaaaggag gcgaggttct aagccattcg 1500
ctcctgctgc ttcacaaaaa ggaagatgga atttggtcca ctgatatttt aaaggaccag 1560
aaagaaccca aaaataagac ctttctaaga tgcgaggcca agaattattc tggacgtttc 1620
acctgctggt ggctgacgac aatcagtact gatttgacat tcagtgtcaa aagcagcaga 1680
ggctcttctg acccccaagg ggtgacgtgc ggagctgcta cactctctgc agagagagtc 1740
agaggggaca acaaggagta tgagtactca gtggagtgcc aggaggacag tgcctgccca 1800
gctgctgagg agagtctgcc cattgaggtc atggtggatg ccgttcacaa gctcaagtat 1860
gaaaactaca ccagcagctt cttcatcagg gacatcatca aacctgaccc acccaagaac 1920
ttgcagctga agccattaaa gaattctcgg caggtggagg tcagctggga gtaccctgac 1980
acctggagta ctccacattc ctacttctcc ctgacattct gcgttcaggt ccagggcaag 2040
agcaagagag aaaagaaaga tagagtcttc acggacaaga cctcagccac ggtcatctgc 2100
cgcaaaaatg ccagcattag cgtgcgggcc caggaccgct actatagctc atcttggagc 2160
gaatgggcat ctgtgccctg cagtgagggc agaggcagcc tgctgacctg cggcgacgtc 2220
gaggagaacc ccgggcccat gggggcaggt gccaccggcc gcgccatgga cgggccgcgc 2280
ctgctgctgt tgctgcttct gggggtgtcc cttggaggtg ccaaggaggc atgccccaca 2340
ggcctgtaca cacacagcgg tgagtgctgc aaagcctgca acctgggcga gggtgtggcc 2400
cagccttgtg gagccaacca gaccgtgtgt gagccctgcc tggacagcgt gacgttctcc 2460
gacgtggtga gcgcgaccga gccgtgcaag ccgtgcaccg agtgcgtggg gctccagagc 2520
atgtcggcgc cgtgcgtgga ggccgatgac gccgtgtgcc gctgcgccta cggctactac 2580
caggatgaga cgactgggcg ctgcgaggcg tgccgcgtgt gcgaggcggg ctcgggcctc 2640
gtgttctcct gccaggacaa gcagaacacc gtgtgcgagg agtgccccga cggcacgtat 2700
tccgacgagg ccaaccacgt ggacccgtgc ctgccctgca ccgtgtgcga ggacaccgag 2760
cgccagctcc gcgagtgcac acgctgggcc gacgccgagt gcgaggagat ccctggccgt 2820
tggattacac ggtccacacc cccagagggc tcggacagca cagcccccag cacccaggag 2880
cctgaggcac ctccagaaca agacctcata gccagcacgg tggcaggtgt ggtgaccaca 2940
gtgatgggca gctcccagcc cgtggtgacc cgaggcacca ccgacaacct catccctgtc 3000
tattgctcca tcctggctgc tgtggttgtg ggtcttgtgg cctacatagc cttcaagagg 3060
tgatctagag ggcccgttta aacccgctga tcagcctcga ctgtgccttc tagttgccag 3120
ccatctgttg tttgcccctc ccccgtgcct tccttgaccc tggaaggtgc cactcccact 3180
gtcctttcct aataaaatga ggaaattgca tcgcattgtc tgagtaggtg tcattctatt 3240
ctggggggtg gggtggggca ggacagcaag ggggaggatt gggaagacaa tagcaggcat 3300
gctggggatg cggtgggctc tatgactagt ggcgaattcg gcgcagatca aagagagcct 3360
gcgggcagag ctcagggtga caggtgcggc ctcggaggcc ccggggcagg ggtgagctga 3420
gccggtcctg gggtgggtgt cccctcctgc acaggatcag gagctccagg gtcgtagggc 3480
agggaccccc cagctccagt ccagggctct gtcctgcacc tggggaatgg tgaccggcat 3540
ctctgtcctc tagctctgga agcaccccag cccctctagt ctgccctcac ccctgaccct 3600
gaccctccac cctgaccccg tcctaacccc tgacctttg 3639
<210> 36
<211> 3017
<212> DNA
<213> artificial sequence
<220>
<223> Inserted matrice TRAC locus_CubiCAR CD22 (60 nucleotides upstream and downstream)
<400> 36
atgagatcat gtcctaaccc tgatcctctt gtcccacaga tatccagaac cctgaccctg 60
ttgctgggcc tttttcccat gcctgccttt actctgccag agttatattg ctggggtttt 120
gaagaagatc ctattaaata aaagaataag cagtattatt aagtagccct gcatttcagg 180
tttccttgag tggcaggcca ggcctggccg tgaacgttca ctgaaatcat ggcctcttgg 240
ccaagattga tagcttgtgc ctgtccctga gtcccagtcc atcacgagca gctggtttct 300
aagatgctat ttcccgtata aagcatgaga ccgtgacttg ccagccccac agagccccgc 360
ccttgtccat cactggcatc tggactccag cctgggttgg ggcaaagagg gaaatgagat 420
catgtcctaa ccctgatcct cttgtcccac agatatccag tacccctacg acgtgcccga 480
ctacgcctcc ggtgagggca gaggaagtct tctaacatgc ggtgacgtgg aggagaatcc 540
gggccccgga tccgctctgc ccgtcaccgc tctgctgctg ccactggcac tgctgctgca 600
cgctgctagg cccggagggg gaggcagctg cccctacagc aaccccagcc tgtgcagcgg 660
aggcggcggc agcggcggag ggggtagcca ggtgcagctg cagcagagcg gccctggcct 720
ggtgaagcca agccagacac tgtccctgac ctgcgccatc agcggcgatt ccgtgagctc 780
caactccgcc gcctggaatt ggatcaggca gtccccttct cggggcctgg agtggctggg 840
aaggacatac tatcggtcta agtggtacaa cgattatgcc gtgtctgtga agagcagaat 900
cacaatcaac cctgacacct ccaagaatca gttctctctg cagctgaata gcgtgacacc 960
agaggacacc gccgtgtact attgcgccag ggaggtgacc ggcgacctgg aggatgcctt 1020
tgacatctgg ggccagggca caatggtgac cgtgagctcc ggaggcggcg gatctggcgg 1080
aggaggaagt gggggcggcg ggagtgatat ccagatgaca cagtccccat cctctctgag 1140
cgcctccgtg ggcgacagag tgacaatcac ctgtagggcc tcccagacca tctggtctta 1200
cctgaactgg tatcagcaga ggcccggcaa ggcccctaat ctgctgatct acgcagcaag 1260
ctccctgcag agcggagtgc catccagatt ctctggcagg ggctccggca cagacttcac 1320
cctgaccatc tctagcctgc aggccgagga cttcgccacc tactattgcc agcagtctta 1380
tagcatcccc cagacatttg gccagggcac caagctggag atcaagtcgg atcccggaag 1440
cggaggggga ggcagctgcc cctacagcaa ccccagcctg tgcagcggag gcggcggcag 1500
cgagctgccc acccagggca ccttctccaa cgtgtccacc aacgtgagcc cagccaagcc 1560
caccaccacc gcctgtcctt attccaatcc ttccctgtgt gctcccacca caacccccgc 1620
tccaaggccc cctacccccg caccaactat tgcctcccag ccactctcac tgcggcctga 1680
ggcctgtcgg cccgctgctg gaggcgcagt gcatacaagg ggcctcgatt tcgcctgcga 1740
tatttacatc tgggcacccc tcgccggcac ctgcggggtg cttctcctct ccctggtgat 1800
taccctgtat tgcagacggg gccggaagaa gctcctctac atttttaagc agcctttcat 1860
gcggccagtg cagacaaccc aagaggagga tgggtgttcc tgcagattcc ctgaggaaga 1920
ggaaggcggg tgcgagctga gagtgaagtt ctccaggagc gcagatgccc ccgcctatca 1980
acagggccag aaccagctct acaacgagct taacctcggg aggcgcgaag aatacgacgt 2040
gttggataag agaagggggc gggaccccga gatgggagga aagccccgga ggaagaaccc 2100
tcaggagggc ctgtacaacg agctgcagaa ggataagatg gccgaggcct actcagagat 2160
cgggatgaag ggggagcggc gccgcgggaa ggggcacgat gggctctacc aggggctgag 2220
cacagccaca aaggacacat acgacgcctt gcacatgcag gcccttccac cccgggaata 2280
gtctagaggg cccgtttaaa cccgctgatc agcctcgact gtgccttcta gttgccagcc 2340
atctgttgtt tgcccctccc ccgtgccttc cttgaccctg gaaggtgcca ctcccactgt 2400
cctttcctaa taaaatgagg aaattgcatc gcattgtctg agtaggtgtc attctattct 2460
ggggggtggg gtggggcagg acagcaaggg ggaggattgg gaagacaata gcaggcatgc 2520
tggggatgcg gtgggctcta tgactagtgg cgaattcccg tgtaccagct gagagactct 2580
aaatccagtg acaagtctgt ctgcctattc accgattttg attctcaaac aaatgtgtca 2640
caaagtaagg attctgatgt gtatatcaca gacaaaactg tgctagacat gaggtctatg 2700
gacttcaaga gcaacagtgc tgtggcctgg agcaacaaat ctgactttgc atgtgcaaac 2760
gccttcaaca acagcattat tccagaagac accttcttcc ccagcccagg taagggcagc 2820
tttggtgcct tcgcaggctg tttccttgct tcaggaatgg ccaggttctg cccagagctc 2880
tggtcaatga tgtctaaaac tcctctgatt ggtggtctcg gccttatcca ttgccaccaa 2940
aaccctcttt ttactaagaa acagtgagcc ttgttctggc agtccagaga atgacacggg 3000
aaaaaagcag atgaaga 3017
<210> 37
<211> 2808
<212> DNA
<213> artificial sequence
<220>
<223> Inserted matrice CD25 locus_IL15_2A_sIL15Ra (60 nucleotides upstream and downstream)
<400> 37
agtgctggct agaaaccaag tgctttactg catgcacatc atttagcaca gttagttgct 60
gtttattatt cctgttccac agctattgtc tgccatataa aaacttaggc caggcacagt 120
ggctcacacc tgtaatccca gcactttgga aggccgaggc aggcagatca caaggtcagg 180
agttcgagac cagcctggcc aacatagcaa aaccccatct ctactaaaaa tacaaaaatt 240
agccaggcat ggtggcgtgt gcactggttt agagtgagga ccacattttt ttggtgccgt 300
gttacacata tgaccgtgac tttgttacac cactacagga ggaagagtag aagaacaatc 360
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 420
tccaacccag ggcccggtac cgggtccgcc accatggact ggacctggat tctgttcctc 480
gtggctgctg ctacaagagt gcacagcggc attcatgtct tcattttggg ctgtttcagt 540
gcagggcttc ctaaaacaga agccaactgg gtgaatgtaa taagtgattt gaaaaaaatt 600
gaagatctta ttcaatctat gcatattgat gctactttat atacggaaag tgatgttcac 660
cccagttgca aagtaacagc aatgaagtgc tttctcttgg agttacaagt tatttcactt 720
gagtccggag atgcaagtat tcatgataca gtagaaaatc tgatcatcct agcaaacaac 780
agtttgtctt ctaatgggaa tgtaacagaa tctggatgca aagaatgtga ggaactggag 840
gaaaaaaata ttaaagaatt tttgcagagt tttgtacata ttgtccaaat gttcatcaac 900
acttctggaa gcggagctac taacttcagc ctgctgaagc aggctggaga cgtggaggag 960
aaccctggac ctgggaccgg ctctgcaacc atggattgga cgtggatcct gtttctcgtg 1020
gcagctgcca caagagttca cagtatcacg tgccctcccc ccatgtccgt ggaacacgca 1080
gacatctggg tcaagagcta cagcttgtac tccagggagc ggtacatttg taactctggt 1140
ttcaagcgta aagccggcac gtccagcctg acggagtgcg tgttgaacaa ggccacgaat 1200
gtcgcccact ggacaacccc cagtctcaaa tgcattagag accctgccct ggttcaccaa 1260
aggccagcgc caccctccac agtaacgacg gcaggggtga ccccacagcc agagagcctc 1320
tccccttctg gaaaagagcc cgcagcttca tctcccagct caaacaacac agcggccaca 1380
acagcagcta ttgtcccggg ctcccagctg atgccttcaa aatcaccttc cacaggaacc 1440
acagagataa gcagtcatga gtcctcccac ggcaccccct ctcagacaac agccaagaac 1500
tgggaactca cagcatccgc ctcccaccag ccgccaggtg tgtatccaca gggccacagc 1560
gacaccactg agggcagagg cagcctgctg acctgcggcg acgtcgagga gaaccccggg 1620
cccatggggg caggtgccac cggccgcgcc atggacgggc cgcgcctgct gctgttgctg 1680
cttctggggg tgtcccttgg aggtgccaag gaggcatgcc ccacaggcct gtacacacac 1740
agcggtgagt gctgcaaagc ctgcaacctg ggcgagggtg tggcccagcc ttgtggagcc 1800
aaccagaccg tgtgtgagcc ctgcctggac agcgtgacgt tctccgacgt ggtgagcgcg 1860
accgagccgt gcaagccgtg caccgagtgc gtggggctcc agagcatgtc ggcgccgtgc 1920
gtggaggccg atgacgccgt gtgccgctgc gcctacggct actaccagga tgagacgact 1980
gggcgctgcg aggcgtgccg cgtgtgcgag gcgggctcgg gcctcgtgtt ctcctgccag 2040
gacaagcaga acaccgtgtg cgaggagtgc cccgacggca cgtattccga cgaggccaac 2100
cacgtggacc cgtgcctgcc ctgcaccgtg tgcgaggaca ccgagcgcca gctccgcgag 2160
tgcacacgct gggccgacgc cgagtgcgag gagatccctg gccgttggat tacacggtcc 2220
acacccccag agggctcgga cagcacagcc cccagcaccc aggagcctga ggcacctcca 2280
gaacaagacc tcatagccag cacggtggca ggtgtggtga ccacagtgat gggcagctcc 2340
cagcccgtgg tgacccgagg caccaccgac aacctcatcc ctgtctattg ctccatcctg 2400
gctgctgtgg ttgtgggtct tgtggcctac atagccttca agaggtgaaa aaccaaaaga 2460
acaagaattt cttggtaaga agccgggaac agacaacaga agtcatgaag cccaagtgaa 2520
atcaaaggtg ctaaatggtc gcccaggaga catccgttgt gcttgcctgc gttttggaag 2580
ctctgaagtc acatcacagg acacggggca gtggcaacct tgtctctatg ccagctcagt 2640
cccatcagag agcgagcgct acccacttct aaatagcaat ttcgccgttg aagaggaagg 2700
gcaaaaccac tagaactctc catcttattt tcatgtatat gtgttcatta aagcatgaat 2760
ggtatggaac tctctccacc ctatatgtag tataaagaaa agtaggtt 2808
<210> 38
<211> 3084
<212> DNA
<213> artificial sequence
<220>
<223> Inserted matrice PD1 locus_IL15_2A_sIL15Ra (60 nucleotides upstream and downstream)
<400> 38
ggtggccggg gaggctttgt ggggccaccc agccccttcc tcacctctct ccatctctca 60
gactccccag acaggccctg gaaccccccc accttctccc cagccctgct cgtggtgacc 120
gaaggggaca acgccacctt cacctgcagc ttctccaaca catcggagag cttcgtgcta 180
aactggtacc gcatgagccc cagcaaccag acggacaagc tggccgcctt ccccgaggac 240
cgcagccagc ccggccagga ctgccgcttc cgtgtcacac aactgcccaa cgggcgtgac 300
ttccacatga gcgtggtcag ggcccggcgc aatgacagcg gcacctacct ctgtggggcc 360
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 420
tccaacccag ggcccggtac cgggtccgcc accatggact ggacctggat tctgttcctc 480
gtggctgctg ctacaagagt gcacagcggc attcatgtct tcattttggg ctgtttcagt 540
gcagggcttc ctaaaacaga agccaactgg gtgaatgtaa taagtgattt gaaaaaaatt 600
gaagatctta ttcaatctat gcatattgat gctactttat atacggaaag tgatgttcac 660
cccagttgca aagtaacagc aatgaagtgc tttctcttgg agttacaagt tatttcactt 720
gagtccggag atgcaagtat tcatgataca gtagaaaatc tgatcatcct agcaaacaac 780
agtttgtctt ctaatgggaa tgtaacagaa tctggatgca aagaatgtga ggaactggag 840
gaaaaaaata ttaaagaatt tttgcagagt tttgtacata ttgtccaaat gttcatcaac 900
acttctggaa gcggagctac taacttcagc ctgctgaagc aggctggaga cgtggaggag 960
aaccctggac ctgggaccgg ctctgcaacc atggattgga cgtggatcct gtttctcgtg 1020
gcagctgcca caagagttca cagtatcacg tgccctcccc ccatgtccgt ggaacacgca 1080
gacatctggg tcaagagcta cagcttgtac tccagggagc ggtacatttg taactctggt 1140
ttcaagcgta aagccggcac gtccagcctg acggagtgcg tgttgaacaa ggccacgaat 1200
gtcgcccact ggacaacccc cagtctcaaa tgcattagag accctgccct ggttcaccaa 1260
aggccagcgc caccctccac agtaacgacg gcaggggtga ccccacagcc agagagcctc 1320
tccccttctg gaaaagagcc cgcagcttca tctcccagct caaacaacac agcggccaca 1380
acagcagcta ttgtcccggg ctcccagctg atgccttcaa aatcaccttc cacaggaacc 1440
acagagataa gcagtcatga gtcctcccac ggcaccccct ctcagacaac agccaagaac 1500
tgggaactca cagcatccgc ctcccaccag ccgccaggtg tgtatccaca gggccacagc 1560
gacaccactg agggcagagg cagcctgctg acctgcggcg acgtcgagga gaaccccggg 1620
cccatggggg caggtgccac cggccgcgcc atggacgggc cgcgcctgct gctgttgctg 1680
cttctggggg tgtcccttgg aggtgccaag gaggcatgcc ccacaggcct gtacacacac 1740
agcggtgagt gctgcaaagc ctgcaacctg ggcgagggtg tggcccagcc ttgtggagcc 1800
aaccagaccg tgtgtgagcc ctgcctggac agcgtgacgt tctccgacgt ggtgagcgcg 1860
accgagccgt gcaagccgtg caccgagtgc gtggggctcc agagcatgtc ggcgccgtgc 1920
gtggaggccg atgacgccgt gtgccgctgc gcctacggct actaccagga tgagacgact 1980
gggcgctgcg aggcgtgccg cgtgtgcgag gcgggctcgg gcctcgtgtt ctcctgccag 2040
gacaagcaga acaccgtgtg cgaggagtgc cccgacggca cgtattccga cgaggccaac 2100
cacgtggacc cgtgcctgcc ctgcaccgtg tgcgaggaca ccgagcgcca gctccgcgag 2160
tgcacacgct gggccgacgc cgagtgcgag gagatccctg gccgttggat tacacggtcc 2220
acacccccag agggctcgga cagcacagcc cccagcaccc aggagcctga ggcacctcca 2280
gaacaagacc tcatagccag cacggtggca ggtgtggtga ccacagtgat gggcagctcc 2340
cagcccgtgg tgacccgagg caccaccgac aacctcatcc ctgtctattg ctccatcctg 2400
gctgctgtgg ttgtgggtct tgtggcctac atagccttca agaggtgatc tagagggccc 2460
gtttaaaccc gctgatcagc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc 2520
ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa 2580
aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg 2640
gggcaggaca gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg 2700
ggctctatga ctagtggcga attcggcgca gatcaaagag agcctgcggg cagagctcag 2760
ggtgacaggt gcggcctcgg aggccccggg gcaggggtga gctgagccgg tcctggggtg 2820
ggtgtcccct cctgcacagg atcaggagct ccagggtcgt agggcaggga ccccccagct 2880
ccagtccagg gctctgtcct gcacctgggg aatggtgacc ggcatctctg tcctctagct 2940
ctggaagcac cccagcccct ctagtctgcc ctcacccctg accctgaccc tccaccctga 3000
ccccgtccta acccctgacc tttgtgccct tccagagaga agggcagaag tgcccacagc 3060
ccaccccagc ccctcaccca ggcc 3084
<210> 39
<211> 3475
<212> DNA
<213> artificial sequence
<220>
<223> Inserted matrice CD25 locus_IL12a_2A_IL12b (60 nucleotides upstream and downstream)
<400> 39
agtgctggct agaaaccaag tgctttactg catgcacatc atttagcaca gttagttgct 60
gtttattatt cctgttccac agctattgtc tgccatataa aaacttaggc caggcacagt 120
ggctcacacc tgtaatccca gcactttgga aggccgaggc aggcagatca caaggtcagg 180
agttcgagac cagcctggcc aacatagcaa aaccccatct ctactaaaaa tacaaaaatt 240
agccaggcat ggtggcgtgt gcactggttt agagtgagga ccacattttt ttggtgccgt 300
gttacacata tgaccgtgac tttgttacac cactacagga ggaagagtag aagaacaatc 360
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 420
tccaacccag ggcccatgtg gccccctggg tcagcctccc agccaccgcc ctcacctgcc 480
gcggccacag gtctgcatcc agcggctcgc cctgtgtccc tgcagtgccg gctcagcatg 540
tgtccagcgc gcagcctcct ccttgtggct accctggtcc tcctggacca cctcagtttg 600
gccagaaacc tccccgtggc cactccagac ccaggaatgt tcccatgcct tcaccactcc 660
caaaacctgc tgagggccgt cagcaacatg ctccagaagg ccagacaaac tctagaattt 720
tacccttgca cttctgaaga gattgatcat gaagatatca caaaagataa aaccagcaca 780
gtggaggcct gtttaccatt ggaattaacc aagaatgaga gttgcctaaa ttccagagag 840
acctctttca taactaatgg gagttgcctg gcctccagaa agacctcttt tatgatggcc 900
ctgtgcctta gtagtattta tgaagacttg aagatgtacc aggtggagtt caagaccatg 960
aatgcaaagc ttctgatgga tcctaagagg cagatctttc tagatcaaaa catgctggca 1020
gttattgatg agctgatgca ggccctgaat ttcaacagtg agactgtgcc acaaaaatcc 1080
tcccttgaag aaccggattt ttataaaact aaaatcaagc tctgcatact tcttcatgct 1140
ttcagaattc gggcagtgac tattgataga gtgatgagct atctgaatgc ttccggaagc 1200
ggagctacta acttcagcct gctgaagcag gctggagacg tggaggagaa ccctggacct 1260
atgtgtcacc agcagttggt catctcttgg ttttccctgg tttttctggc atctcccctc 1320
gtggccatat gggaactgaa gaaagatgtt tatgtcgtag aattggattg gtatccggat 1380
gcccctggag aaatggtggt cctcacctgt gacacccctg aagaagatgg tatcacctgg 1440
accttggacc agagcagtga ggtcttaggc tctggcaaaa ccctgaccat ccaagtcaaa 1500
gagtttggag atgctggcca gtacacctgt cacaaaggag gcgaggttct aagccattcg 1560
ctcctgctgc ttcacaaaaa ggaagatgga atttggtcca ctgatatttt aaaggaccag 1620
aaagaaccca aaaataagac ctttctaaga tgcgaggcca agaattattc tggacgtttc 1680
acctgctggt ggctgacgac aatcagtact gatttgacat tcagtgtcaa aagcagcaga 1740
ggctcttctg acccccaagg ggtgacgtgc ggagctgcta cactctctgc agagagagtc 1800
agaggggaca acaaggagta tgagtactca gtggagtgcc aggaggacag tgcctgccca 1860
gctgctgagg agagtctgcc cattgaggtc atggtggatg ccgttcacaa gctcaagtat 1920
gaaaactaca ccagcagctt cttcatcagg gacatcatca aacctgaccc acccaagaac 1980
ttgcagctga agccattaaa gaattctcgg caggtggagg tcagctggga gtaccctgac 2040
acctggagta ctccacattc ctacttctcc ctgacattct gcgttcaggt ccagggcaag 2100
agcaagagag aaaagaaaga tagagtcttc acggacaaga cctcagccac ggtcatctgc 2160
cgcaaaaatg ccagcattag cgtgcgggcc caggaccgct actatagctc atcttggagc 2220
gaatgggcat ctgtgccctg cagtgagggc agaggcagcc tgctgacctg cggcgacgtc 2280
gaggagaacc ccgggcccat gggggcaggt gccaccggcc gcgccatgga cgggccgcgc 2340
ctgctgctgt tgctgcttct gggggtgtcc cttggaggtg ccaaggaggc atgccccaca 2400
ggcctgtaca cacacagcgg tgagtgctgc aaagcctgca acctgggcga gggtgtggcc 2460
cagccttgtg gagccaacca gaccgtgtgt gagccctgcc tggacagcgt gacgttctcc 2520
gacgtggtga gcgcgaccga gccgtgcaag ccgtgcaccg agtgcgtggg gctccagagc 2580
atgtcggcgc cgtgcgtgga ggccgatgac gccgtgtgcc gctgcgccta cggctactac 2640
caggatgaga cgactgggcg ctgcgaggcg tgccgcgtgt gcgaggcggg ctcgggcctc 2700
gtgttctcct gccaggacaa gcagaacacc gtgtgcgagg agtgccccga cggcacgtat 2760
tccgacgagg ccaaccacgt ggacccgtgc ctgccctgca ccgtgtgcga ggacaccgag 2820
cgccagctcc gcgagtgcac acgctgggcc gacgccgagt gcgaggagat ccctggccgt 2880
tggattacac ggtccacacc cccagagggc tcggacagca cagcccccag cacccaggag 2940
cctgaggcac ctccagaaca agacctcata gccagcacgg tggcaggtgt ggtgaccaca 3000
gtgatgggca gctcccagcc cgtggtgacc cgaggcacca ccgacaacct catccctgtc 3060
tattgctcca tcctggctgc tgtggttgtg ggtcttgtgg cctacatagc cttcaagagg 3120
tgaaaaacca aaagaacaag aatttcttgg taagaagccg ggaacagaca acagaagtca 3180
tgaagcccaa gtgaaatcaa aggtgctaaa tggtcgccca ggagacatcc gttgtgcttg 3240
cctgcgtttt ggaagctctg aagtcacatc acaggacacg gggcagtggc aaccttgtct 3300
ctatgccagc tcagtcccat cagagagcga gcgctaccca cttctaaata gcaatttcgc 3360
cgttgaagag gaagggcaaa accactagaa ctctccatct tattttcatg tatatgtgtt 3420
catgaatggt atggaactct ctccacccta tatgtagtat aaagaaaagt aggtt 3475
<210> 40
<211> 3759
<212> DNA
<213> artificial sequence
<220>
<223> Inserted matrice PD1 locus_IL12a_2A_IL12b (60 nucleotides upstream and downstream)
<400> 40
ggtggccggg gaggctttgt ggggccaccc agccccttcc tcacctctct ccatctctca 60
gactccccag acaggccctg gaaccccccc accttctccc cagccctgct cgtggtgacc 120
gaaggggaca acgccacctt cacctgcagc ttctccaaca catcggagag cttcgtgcta 180
aactggtacc gcatgagccc cagcaaccag acggacaagc tggccgcctt ccccgaggac 240
cgcagccagc ccggccagga ctgccgcttc cgtgtcacac aactgcccaa cgggcgtgac 300
ttccacatga gcgtggtcag ggcccggcgc aatgacagcg gcacctacct ctgtggggcc 360
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 420
tccaacccag ggcccatgtg gccccctggg tcagcctccc agccaccgcc ctcacctgcc 480
gcggccacag gtctgcatcc agcggctcgc cctgtgtccc tgcagtgccg gctcagcatg 540
tgtccagcgc gcagcctcct ccttgtggct accctggtcc tcctggacca cctcagtttg 600
gccagaaacc tccccgtggc cactccagac ccaggaatgt tcccatgcct tcaccactcc 660
caaaacctgc tgagggccgt cagcaacatg ctccagaagg ccagacaaac tctagaattt 720
tacccttgca cttctgaaga gattgatcat gaagatatca caaaagataa aaccagcaca 780
gtggaggcct gtttaccatt ggaattaacc aagaatgaga gttgcctaaa ttccagagag 840
acctctttca taactaatgg gagttgcctg gcctccagaa agacctcttt tatgatggcc 900
ctgtgcctta gtagtattta tgaagacttg aagatgtacc aggtggagtt caagaccatg 960
aatgcaaagc ttctgatgga tcctaagagg cagatctttc tagatcaaaa catgctggca 1020
gttattgatg agctgatgca ggccctgaat ttcaacagtg agactgtgcc acaaaaatcc 1080
tcccttgaag aaccggattt ttataaaact aaaatcaagc tctgcatact tcttcatgct 1140
ttcagaattc gggcagtgac tattgataga gtgatgagct atctgaatgc ttccggaagc 1200
ggagctacta acttcagcct gctgaagcag gctggagacg tggaggagaa ccctggacct 1260
atgtgtcacc agcagttggt catctcttgg ttttccctgg tttttctggc atctcccctc 1320
gtggccatat gggaactgaa gaaagatgtt tatgtcgtag aattggattg gtatccggat 1380
gcccctggag aaatggtggt cctcacctgt gacacccctg aagaagatgg tatcacctgg 1440
accttggacc agagcagtga ggtcttaggc tctggcaaaa ccctgaccat ccaagtcaaa 1500
gagtttggag atgctggcca gtacacctgt cacaaaggag gcgaggttct aagccattcg 1560
ctcctgctgc ttcacaaaaa ggaagatgga atttggtcca ctgatatttt aaaggaccag 1620
aaagaaccca aaaataagac ctttctaaga tgcgaggcca agaattattc tggacgtttc 1680
acctgctggt ggctgacgac aatcagtact gatttgacat tcagtgtcaa aagcagcaga 1740
ggctcttctg acccccaagg ggtgacgtgc ggagctgcta cactctctgc agagagagtc 1800
agaggggaca acaaggagta tgagtactca gtggagtgcc aggaggacag tgcctgccca 1860
gctgctgagg agagtctgcc cattgaggtc atggtggatg ccgttcacaa gctcaagtat 1920
gaaaactaca ccagcagctt cttcatcagg gacatcatca aacctgaccc acccaagaac 1980
ttgcagctga agccattaaa gaattctcgg caggtggagg tcagctggga gtaccctgac 2040
acctggagta ctccacattc ctacttctcc ctgacattct gcgttcaggt ccagggcaag 2100
agcaagagag aaaagaaaga tagagtcttc acggacaaga cctcagccac ggtcatctgc 2160
cgcaaaaatg ccagcattag cgtgcgggcc caggaccgct actatagctc atcttggagc 2220
gaatgggcat ctgtgccctg cagtgagggc agaggcagcc tgctgacctg cggcgacgtc 2280
gaggagaacc ccgggcccat gggggcaggt gccaccggcc gcgccatgga cgggccgcgc 2340
ctgctgctgt tgctgcttct gggggtgtcc cttggaggtg ccaaggaggc atgccccaca 2400
ggcctgtaca cacacagcgg tgagtgctgc aaagcctgca acctgggcga gggtgtggcc 2460
cagccttgtg gagccaacca gaccgtgtgt gagccctgcc tggacagcgt gacgttctcc 2520
gacgtggtga gcgcgaccga gccgtgcaag ccgtgcaccg agtgcgtggg gctccagagc 2580
atgtcggcgc cgtgcgtgga ggccgatgac gccgtgtgcc gctgcgccta cggctactac 2640
caggatgaga cgactgggcg ctgcgaggcg tgccgcgtgt gcgaggcggg ctcgggcctc 2700
gtgttctcct gccaggacaa gcagaacacc gtgtgcgagg agtgccccga cggcacgtat 2760
tccgacgagg ccaaccacgt ggacccgtgc ctgccctgca ccgtgtgcga ggacaccgag 2820
cgccagctcc gcgagtgcac acgctgggcc gacgccgagt gcgaggagat ccctggccgt 2880
tggattacac ggtccacacc cccagagggc tcggacagca cagcccccag cacccaggag 2940
cctgaggcac ctccagaaca agacctcata gccagcacgg tggcaggtgt ggtgaccaca 3000
gtgatgggca gctcccagcc cgtggtgacc cgaggcacca ccgacaacct catccctgtc 3060
tattgctcca tcctggctgc tgtggttgtg ggtcttgtgg cctacatagc cttcaagagg 3120
tgatctagag ggcccgttta aacccgctga tcagcctcga ctgtgccttc tagttgccag 3180
ccatctgttg tttgcccctc ccccgtgcct tccttgaccc tggaaggtgc cactcccact 3240
gtcctttcct aataaaatga ggaaattgca tcgcattgtc tgagtaggtg tcattctatt 3300
ctggggggtg gggtggggca ggacagcaag ggggaggatt gggaagacaa tagcaggcat 3360
gctggggatg cggtgggctc tatgactagt ggcgaattcg gcgcagatca aagagagcct 3420
gcgggcagag ctcagggtga caggtgcggc ctcggaggcc ccggggcagg ggtgagctga 3480
gccggtcctg gggtgggtgt cccctcctgc acaggatcag gagctccagg gtcgtagggc 3540
agggaccccc cagctccagt ccagggctct gtcctgcacc tggggaatgg tgaccggcat 3600
ctctgtcctc tagctctgga agcaccccag cccctctagt ctgccctcac ccctgaccct 3660
gaccctccac cctgaccccg tcctaacccc tgacctttgt gcccttccag agagaagggc 3720
agaagtgccc acagcccacc ccagcccctc acccaggcc 3759
<210> 41
<211> 60
<212> DNA
<213> artificial sequence
<220>
<223> upstream TRAC locus polynucleotide sequence
<400> 41
atgagatcat gtcctaaccc tgatcctctt gtcccacaga tatccagaac cctgaccctg 60
<210> 42
<211> 60
<212> DNA
<213> artificial sequence
<220>
<223> downstream TRAC locus polynucleotide sequence
<400> 42
gaaacagtga gccttgttct ggcagtccag agaatgacac gggaaaaaag cagatgaaga 60
<210> 43
<211> 60
<212> DNA
<213> artificial sequence
<220>
<223> upstream CD25 locus polynucleotide sequence
<400> 43
agtgctggct agaaaccaag tgctttactg catgcacatc atttagcaca gttagttgct 60
<210> 44
<211> 52
<212> DNA
<213> artificial sequence
<220>
<223> downstream CD25 locus polynucleotide sequence
<400> 44
gaatggtatg gaactctctc caccctatat gtagtataaa gaaaagtagg tt 52
<210> 45
<211> 60
<212> DNA
<213> artificial sequence
<220>
<223> upstream PD1 locus polynucleotide sequence
<400> 45
ggtggccggg gaggctttgt ggggccaccc agccccttcc tcacctctct ccatctctca 60
<210> 46
<211> 60
<212> DNA
<213> artificial sequence
<220>
<223> downstream PD1 locus polynucleotide sequence
<400> 46
tgcccttcca gagagaaggg cagaagtgcc cacagcccac cccagcccct cacccaggcc 60
<210> 47
<211> 759
<212> DNA
<213> artificial sequence
<220>
<223> IL-12a polynucleotide
<400> 47
atgtggcccc ctgggtcagc ctcccagcca ccgccctcac ctgccgcggc cacaggtctg 60
catccagcgg ctcgccctgt gtccctgcag tgccggctca gcatgtgtcc agcgcgcagc 120
ctcctccttg tggctaccct ggtcctcctg gaccacctca gtttggccag aaacctcccc 180
gtggccactc cagacccagg aatgttccca tgccttcacc actcccaaaa cctgctgagg 240
gccgtcagca acatgctcca gaaggccaga caaactctag aattttaccc ttgcacttct 300
gaagagattg atcatgaaga tatcacaaaa gataaaacca gcacagtgga ggcctgttta 360
ccattggaat taaccaagaa tgagagttgc ctaaattcca gagagacctc tttcataact 420
aatgggagtt gcctggcctc cagaaagacc tcttttatga tggccctgtg ccttagtagt 480
atttatgaag acttgaagat gtaccaggtg gagttcaaga ccatgaatgc aaagcttctg 540
atggatccta agaggcagat ctttctagat caaaacatgc tggcagttat tgatgagctg 600
atgcaggccc tgaatttcaa cagtgagact gtgccacaaa aatcctccct tgaagaaccg 660
gatttttata aaactaaaat caagctctgc atacttcttc atgctttcag aattcgggca 720
gtgactattg atagagtgat gagctatctg aatgcttcc 759
<210> 48
<211> 984
<212> DNA
<213> artificial sequence
<220>
<223> IL12b polynucleotide
<400> 48
atgtgtcacc agcagttggt catctcttgg ttttccctgg tttttctggc atctcccctc 60
gtggccatat gggaactgaa gaaagatgtt tatgtcgtag aattggattg gtatccggat 120
gcccctggag aaatggtggt cctcacctgt gacacccctg aagaagatgg tatcacctgg 180
accttggacc agagcagtga ggtcttaggc tctggcaaaa ccctgaccat ccaagtcaaa 240
gagtttggag atgctggcca gtacacctgt cacaaaggag gcgaggttct aagccattcg 300
ctcctgctgc ttcacaaaaa ggaagatgga atttggtcca ctgatatttt aaaggaccag 360
aaagaaccca aaaataagac ctttctaaga tgcgaggcca agaattattc tggacgtttc 420
acctgctggt ggctgacgac aatcagtact gatttgacat tcagtgtcaa aagcagcaga 480
ggctcttctg acccccaagg ggtgacgtgc ggagctgcta cactctctgc agagagagtc 540
agaggggaca acaaggagta tgagtactca gtggagtgcc aggaggacag tgcctgccca 600
gctgctgagg agagtctgcc cattgaggtc atggtggatg ccgttcacaa gctcaagtat 660
gaaaactaca ccagcagctt cttcatcagg gacatcatca aacctgaccc acccaagaac 720
ttgcagctga agccattaaa gaattctcgg caggtggagg tcagctggga gtaccctgac 780
acctggagta ctccacattc ctacttctcc ctgacattct gcgttcaggt ccagggcaag 840
agcaagagag aaaagaaaga tagagtcttc acggacaaga cctcagccac ggtcatctgc 900
cgcaaaaatg ccagcattag cgtgcgggcc caggaccgct actatagctc atcttggagc 960
gaatgggcat ctgtgccctg cagt 984
<210> 49
<211> 399
<212> DNA
<213> artificial sequence
<220>
<223> IL15 polynucleotide
<400> 49
ggcattcatg tcttcatttt gggctgtttc agtgcagggc ttcctaaaac agaagccaac 60
tgggtgaatg taataagtga tttgaaaaaa attgaagatc ttattcaatc tatgcatatt 120
gatgctactt tatatacgga aagtgatgtt caccccagtt gcaaagtaac agcaatgaag 180
tgctttctct tggagttaca agttatttca cttgagtccg gagatgcaag tattcatgat 240
acagtagaaa atctgatcat cctagcaaac aacagtttgt cttctaatgg gaatgtaaca 300
gaatctggat gcaaagaatg tgaggaactg gaggaaaaaa atattaaaga atttttgcag 360
agttttgtac atattgtcca aatgttcatc aacacttct 399
<210> 50
<211> 525
<212> DNA
<213> artificial sequence
<220>
<223> sIL15ra polynucleotide
<400> 50
atcacgtgcc ctccccccat gtccgtggaa cacgcagaca tctgggtcaa gagctacagc 60
ttgtactcca gggagcggta catttgtaac tctggtttca agcgtaaagc cggcacgtcc 120
agcctgacgg agtgcgtgtt gaacaaggcc acgaatgtcg cccactggac aacccccagt 180
ctcaaatgca ttagagaccc tgccctggtt caccaaaggc cagcgccacc ctccacagta 240
acgacggcag gggtgacccc acagccagag agcctctccc cttctggaaa agagcccgca 300
gcttcatctc ccagctcaaa caacacagcg gccacaacag cagctattgt cccgggctcc 360
cagctgatgc cttcaaaatc accttccaca ggaaccacag agataagcag tcatgagtcc 420
tcccacggca ccccctctca gacaacagcc aagaactggg aactcacagc atccgcctcc 480
caccagccgc caggtgtgta tccacagggc cacagcgaca ccact 525
<210> 51
<211> 1818
<212> DNA
<213> artificial sequence
<220>
<223> soluble GP130 polynucleotide
<400> 51
atgctgacac tgcagacttg gctggtgcag gcactgttta tttttctgac tactgaatca 60
actggcgaac tgctggaccc ttgtggctac atcagccctg agtccccagt ggtgcagctg 120
cacagcaact tcaccgccgt gtgcgtgctg aaggagaagt gtatggacta ctttcacgtg 180
aacgccaatt atatcgtgtg gaaaaccaac cacttcacaa tccccaagga gcagtacacc 240
atcatcaata ggacagccag ctccgtgacc tttacagaca tcgcctccct gaacatccag 300
ctgacctgca atatcctgac attcggccag ctggagcaga acgtgtatgg catcaccatc 360
atctctggcc tgccccctga gaagcctaag aacctgagct gcatcgtgaa tgagggcaag 420
aagatgcggt gtgagtggga cggcggcaga gagacacacc tggagacaaa cttcaccctg 480
aagtccgagt gggccacaca caagtttgcc gactgcaagg ccaagcgcga taccccaaca 540
tcctgtaccg tggattactc tacagtgtat tttgtgaaca tcgaagtgtg ggtggaggcc 600
gagaatgccc tgggcaaggt gacctccgac cacatcaact tcgatcccgt gtacaaggtg 660
aagcctaacc caccccacaa tctgagcgtg atcaattccg aggagctgtc tagcatcctg 720
aagctgacct ggacaaaccc atctatcaag agcgtgatca tcctgaagta caatatccag 780
tatcggacca aggacgcctc cacatggagc cagatccctc cagaggatac cgccagcaca 840
agatcctctt tcaccgtgca ggacctgaag cccttcacag agtacgtgtt tcggatcaga 900
tgtatgaagg aggacggcaa gggctactgg agcgattggt ccgaggaggc cagcggcatc 960
acctatgagg acaggccttc taaggccccc agcttctggt acaagatcga tccatcccac 1020
acccagggct atcgcacagt gcagctggtg tggaaaaccc tgcccccttt cgaggccaac 1080
ggcaagatcc tggactacga ggtgaccctg acacggtgga agtcccacct gcagaactat 1140
accgtgaatg ccaccaagct gacagtgaac ctgacaaatg atcggtacct ggccaccctg 1200
acagtgagaa acctggtggg caagtctgac gccgccgtgc tgaccatccc tgcctgcgat 1260
ttccaggcca cacacccagt gatggacctg aaggcctttc ccaaggataa tatgctgtgg 1320
gtggagtgga ccacacctag agagtccgtg aagaagtaca tcctggagtg gtgcgtgctg 1380
tctgacaagg ccccatgtat caccgactgg cagcaggagg atggcaccgt gcacaggaca 1440
tatctgcgcg gcaacctggc cgagtctaag tgttacctga tcaccgtgac acccgtgtat 1500
gcagacggac caggctctcc tgagagcatc aaggcctacc tgaagcaggc accaccaagc 1560
aagggaccaa ccgtgcggac aaagaaggtc ggcaagaatg aggccgtgct ggagtgggac 1620
cagctgcctg tggatgtgca gaacggcttc atcaggaatt acaccatctt ttatcgcaca 1680
atcatcggca acgagacagc cgtgaatgtg gacagctccc acaccgagta tacactgtct 1740
agcctgacct ccgatacact gtacatggtg aggatggccg cctatacaga cgagggcggc 1800
aaggatggcc ccgagttt 1818
<210> 52
<211> 72
<212> DNA
<213> artificial sequence
<220>
<223> IgE signal sequence
<400> 52
ggtaccgggt ccgccaccat ggactggacc tggattctgt tcctcgtggc tgctgctaca 60
agagtgcaca gc 72
<210> 53
<211> 75
<212> DNA
<213> artificial sequence
<220>
<223> F2A
<400> 53
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 60
tccaacccag ggccc 75
<210> 54
<211> 66
<212> DNA
<213> artificial sequence
<220>
<223> P2A
<400> 54
ggaagcggag ctactaactt cagcctgctg aagcaggctg gagacgtgga ggagaaccct 60
ggacct 66
<210> 55
<211> 54
<212> DNA
<213> artificial sequence
<220>
<223> T2A
<400> 55
gagggcagag gcagcctgct gacctgcggc gacgtcgagg agaaccccgg gccc 54
<210> 56
<211> 825
<212> DNA
<213> artificial sequence
<220>
<223> LNGFR
<400> 56
atgggggcag gtgccaccgg ccgcgccatg gacgggccgc gcctgctgct gttgctgctt 60
ctgggggtgt cccttggagg tgccaaggag gcatgcccca caggcctgta cacacacagc 120
ggtgagtgct gcaaagcctg caacctgggc gagggtgtgg cccagccttg tggagccaac 180
cagaccgtgt gtgagccctg cctggacagc gtgacgttct ccgacgtggt gagcgcgacc 240
gagccgtgca agccgtgcac cgagtgcgtg gggctccaga gcatgtcggc gccgtgcgtg 300
gaggccgatg acgccgtgtg ccgctgcgcc tacggctact accaggatga gacgactggg 360
cgctgcgagg cgtgccgcgt gtgcgaggcg ggctcgggcc tcgtgttctc ctgccaggac 420
aagcagaaca ccgtgtgcga ggagtgcccc gacggcacgt attccgacga ggccaaccac 480
gtggacccgt gcctgccctg caccgtgtgc gaggacaccg agcgccagct ccgcgagtgc 540
acacgctggg ccgacgccga gtgcgaggag atccctggcc gttggattac acggtccaca 600
cccccagagg gctcggacag cacagccccc agcacccagg agcctgaggc acctccagaa 660
caagacctca tagccagcac ggtggcaggt gtggtgacca cagtgatggg cagctcccag 720
cccgtggtga cccgaggcac caccgacaac ctcatccctg tctattgctc catcctggct 780
gctgtggttg tgggtcttgt ggcctacata gccttcaaga ggtga 825
<210> 57
<211> 253
<212> PRT
<213> artificial sequence
<220>
<223> IL-12a polypeptide
<400> 57
Met Trp Pro Pro Gly Ser Ala Ser Gln Pro Pro Pro Ser Pro Ala Ala
1 5 10 15
Ala Thr Gly Leu His Pro Ala Ala Arg Pro Val Ser Leu Gln Cys Arg
20 25 30
Leu Ser Met Cys Pro Ala Arg Ser Leu Leu Leu Val Ala Thr Leu Val
35 40 45
Leu Leu Asp His Leu Ser Leu Ala Arg Asn Leu Pro Val Ala Thr Pro
50 55 60
Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg
65 70 75 80
Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr
85 90 95
Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys
100 105 110
Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu
115 120 125
Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys
130 135 140
Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser
145 150 155 160
Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn
165 170 175
Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn
180 185 190
Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser
195 200 205
Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys
210 215 220
Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala
225 230 235 240
Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser
245 250
<210> 58
<211> 328
<212> PRT
<213> artificial sequence
<220>
<223> IL12b polypeptide
<400> 58
Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu
1 5 10 15
Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val
20 25 30
Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln
50 55 60
Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys
65 70 75 80
Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val
85 90 95
Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp
100 105 110
Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe
115 120 125
Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp
130 135 140
Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg
145 150 155 160
Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser
165 170 175
Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu
180 185 190
Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile
195 200 205
Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr
210 215 220
Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn
225 230 235 240
Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp
245 250 255
Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr
260 265 270
Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg
275 280 285
Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala
290 295 300
Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser
305 310 315 320
Glu Trp Ala Ser Val Pro Cys Ser
325
245 250
<210> 59
<211> 133
<212> PRT
<213> artificial sequence
<220>
<223> IL15 polypeptide
<400> 59
Gly Ile His Val Phe Ile Leu Gly Cys Phe Ser Ala Gly Leu Pro Lys
1 5 10 15
Thr Glu Ala Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu
20 25 30
Asp Leu Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser
35 40 45
Asp Val His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu
50 55 60
Glu Leu Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp
65 70 75 80
Thr Val Glu Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn
85 90 95
Gly Asn Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu
100 105 110
Lys Asn Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met
115 120 125
Phe Ile Asn Thr Ser
130
<210> 60
<211> 175
<212> PRT
<213> artificial sequence
<220>
<223> sIL15ra polypeptide
<400> 60
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val
65 70 75 80
Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly
85 90 95
Lys Glu Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr
100 105 110
Thr Ala Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro
115 120 125
Ser Thr Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr
130 135 140
Pro Ser Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser
145 150 155 160
His Gln Pro Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr
165 170 175
<210> 61
<211> 606
<212> PRT
<213> artificial sequence
<220>
<223> soluble gp130
<400> 61
Met Leu Thr Leu Gln Thr Trp Leu Val Gln Ala Leu Phe Ile Phe Leu
1 5 10 15
Thr Thr Glu Ser Thr Gly Glu Leu Leu Asp Pro Cys Gly Tyr Ile Ser
20 25 30
Pro Glu Ser Pro Val Val Gln Leu His Ser Asn Phe Thr Ala Val Cys
35 40 45
Val Leu Lys Glu Lys Cys Met Asp Tyr Phe His Val Asn Ala Asn Tyr
50 55 60
Ile Val Trp Lys Thr Asn His Phe Thr Ile Pro Lys Glu Gln Tyr Thr
65 70 75 80
Ile Ile Asn Arg Thr Ala Ser Ser Val Thr Phe Thr Asp Ile Ala Ser
85 90 95
Leu Asn Ile Gln Leu Thr Cys Asn Ile Leu Thr Phe Gly Gln Leu Glu
100 105 110
Gln Asn Val Tyr Gly Ile Thr Ile Ile Ser Gly Leu Pro Pro Glu Lys
115 120 125
Pro Lys Asn Leu Ser Cys Ile Val Asn Glu Gly Lys Lys Met Arg Cys
130 135 140
Glu Trp Asp Gly Gly Arg Glu Thr His Leu Glu Thr Asn Phe Thr Leu
145 150 155 160
Lys Ser Glu Trp Ala Thr His Lys Phe Ala Asp Cys Lys Ala Lys Arg
165 170 175
Asp Thr Pro Thr Ser Cys Thr Val Asp Tyr Ser Thr Val Tyr Phe Val
180 185 190
Asn Ile Glu Val Trp Val Glu Ala Glu Asn Ala Leu Gly Lys Val Thr
195 200 205
Ser Asp His Ile Asn Phe Asp Pro Val Tyr Lys Val Lys Pro Asn Pro
210 215 220
Pro His Asn Leu Ser Val Ile Asn Ser Glu Glu Leu Ser Ser Ile Leu
225 230 235 240
Lys Leu Thr Trp Thr Asn Pro Ser Ile Lys Ser Val Ile Ile Leu Lys
245 250 255
Tyr Asn Ile Gln Tyr Arg Thr Lys Asp Ala Ser Thr Trp Ser Gln Ile
260 265 270
Pro Pro Glu Asp Thr Ala Ser Thr Arg Ser Ser Phe Thr Val Gln Asp
275 280 285
Leu Lys Pro Phe Thr Glu Tyr Val Phe Arg Ile Arg Cys Met Lys Glu
290 295 300
Asp Gly Lys Gly Tyr Trp Ser Asp Trp Ser Glu Glu Ala Ser Gly Ile
305 310 315 320
Thr Tyr Glu Asp Arg Pro Ser Lys Ala Pro Ser Phe Trp Tyr Lys Ile
325 330 335
Asp Pro Ser His Thr Gln Gly Tyr Arg Thr Val Gln Leu Val Trp Lys
340 345 350
Thr Leu Pro Pro Phe Glu Ala Asn Gly Lys Ile Leu Asp Tyr Glu Val
355 360 365
Thr Leu Thr Arg Trp Lys Ser His Leu Gln Asn Tyr Thr Val Asn Ala
370 375 380
Thr Lys Leu Thr Val Asn Leu Thr Asn Asp Arg Tyr Leu Ala Thr Leu
385 390 395 400
Thr Val Arg Asn Leu Val Gly Lys Ser Asp Ala Ala Val Leu Thr Ile
405 410 415
Pro Ala Cys Asp Phe Gln Ala Thr His Pro Val Met Asp Leu Lys Ala
420 425 430
Phe Pro Lys Asp Asn Met Leu Trp Val Glu Trp Thr Thr Pro Arg Glu
435 440 445
Ser Val Lys Lys Tyr Ile Leu Glu Trp Cys Val Leu Ser Asp Lys Ala
450 455 460
Pro Cys Ile Thr Asp Trp Gln Gln Glu Asp Gly Thr Val His Arg Thr
465 470 475 480
Tyr Leu Arg Gly Asn Leu Ala Glu Ser Lys Cys Tyr Leu Ile Thr Val
485 490 495
Thr Pro Val Tyr Ala Asp Gly Pro Gly Ser Pro Glu Ser Ile Lys Ala
500 505 510
Tyr Leu Lys Gln Ala Pro Pro Ser Lys Gly Pro Thr Val Arg Thr Lys
515 520 525
Lys Val Gly Lys Asn Glu Ala Val Leu Glu Trp Asp Gln Leu Pro Val
530 535 540
Asp Val Gln Asn Gly Phe Ile Arg Asn Tyr Thr Ile Phe Tyr Arg Thr
545 550 555 560
Ile Ile Gly Asn Glu Thr Ala Val Asn Val Asp Ser Ser His Thr Glu
565 570 575
Tyr Thr Leu Ser Ser Leu Thr Ser Asp Thr Leu Tyr Met Val Arg Met
580 585 590
Ala Ala Tyr Thr Asp Glu Gly Gly Lys Asp Gly Pro Glu Phe
595 600 605
<210> 62
<211> 836
<212> PRT
<213> artificial sequence
<220>
<223> soluble gp130 fused to a Fc
<400> 62
Met Leu Thr Leu Gln Thr Trp Leu Val Gln Ala Leu Phe Ile Phe Leu
1 5 10 15
Thr Thr Glu Ser Thr Gly Glu Leu Leu Asp Pro Cys Gly Tyr Ile Ser
20 25 30
Pro Glu Ser Pro Val Val Gln Leu His Ser Asn Phe Thr Ala Val Cys
35 40 45
Val Leu Lys Glu Lys Cys Met Asp Tyr Phe His Val Asn Ala Asn Tyr
50 55 60
Ile Val Trp Lys Thr Asn His Phe Thr Ile Pro Lys Glu Gln Tyr Thr
65 70 75 80
Ile Ile Asn Arg Thr Ala Ser Ser Val Thr Phe Thr Asp Ile Ala Ser
85 90 95
Leu Asn Ile Gln Leu Thr Cys Asn Ile Leu Thr Phe Gly Gln Leu Glu
100 105 110
Gln Asn Val Tyr Gly Ile Thr Ile Ile Ser Gly Leu Pro Pro Glu Lys
115 120 125
Pro Lys Asn Leu Ser Cys Ile Val Asn Glu Gly Lys Lys Met Arg Cys
130 135 140
Glu Trp Asp Gly Gly Arg Glu Thr His Leu Glu Thr Asn Phe Thr Leu
145 150 155 160
Lys Ser Glu Trp Ala Thr His Lys Phe Ala Asp Cys Lys Ala Lys Arg
165 170 175
Asp Thr Pro Thr Ser Cys Thr Val Asp Tyr Ser Thr Val Tyr Phe Val
180 185 190
Asn Ile Glu Val Trp Val Glu Ala Glu Asn Ala Leu Gly Lys Val Thr
195 200 205
Ser Asp His Ile Asn Phe Asp Pro Val Tyr Lys Val Lys Pro Asn Pro
210 215 220
Pro His Asn Leu Ser Val Ile Asn Ser Glu Glu Leu Ser Ser Ile Leu
225 230 235 240
Lys Leu Thr Trp Thr Asn Pro Ser Ile Lys Ser Val Ile Ile Leu Lys
245 250 255
Tyr Asn Ile Gln Tyr Arg Thr Lys Asp Ala Ser Thr Trp Ser Gln Ile
260 265 270
Pro Pro Glu Asp Thr Ala Ser Thr Arg Ser Ser Phe Thr Val Gln Asp
275 280 285
Leu Lys Pro Phe Thr Glu Tyr Val Phe Arg Ile Arg Cys Met Lys Glu
290 295 300
Asp Gly Lys Gly Tyr Trp Ser Asp Trp Ser Glu Glu Ala Ser Gly Ile
305 310 315 320
Thr Tyr Glu Asp Arg Pro Ser Lys Ala Pro Ser Phe Trp Tyr Lys Ile
325 330 335
Asp Pro Ser His Thr Gln Gly Tyr Arg Thr Val Gln Leu Val Trp Lys
340 345 350
Thr Leu Pro Pro Phe Glu Ala Asn Gly Lys Ile Leu Asp Tyr Glu Val
355 360 365
Thr Leu Thr Arg Trp Lys Ser His Leu Gln Asn Tyr Thr Val Asn Ala
370 375 380
Thr Lys Leu Thr Val Asn Leu Thr Asn Asp Arg Tyr Leu Ala Thr Leu
385 390 395 400
Thr Val Arg Asn Leu Val Gly Lys Ser Asp Ala Ala Val Leu Thr Ile
405 410 415
Pro Ala Cys Asp Phe Gln Ala Thr His Pro Val Met Asp Leu Lys Ala
420 425 430
Phe Pro Lys Asp Asn Met Leu Trp Val Glu Trp Thr Thr Pro Arg Glu
435 440 445
Ser Val Lys Lys Tyr Ile Leu Glu Trp Cys Val Leu Ser Asp Lys Ala
450 455 460
Pro Cys Ile Thr Asp Trp Gln Gln Glu Asp Gly Thr Val His Arg Thr
465 470 475 480
Tyr Leu Arg Gly Asn Leu Ala Glu Ser Lys Cys Tyr Leu Ile Thr Val
485 490 495
Thr Pro Val Tyr Ala Asp Gly Pro Gly Ser Pro Glu Ser Ile Lys Ala
500 505 510
Tyr Leu Lys Gln Ala Pro Pro Ser Lys Gly Pro Thr Val Arg Thr Lys
515 520 525
Lys Val Gly Lys Asn Glu Ala Val Leu Glu Trp Asp Gln Leu Pro Val
530 535 540
Asp Val Gln Asn Gly Phe Ile Arg Asn Tyr Thr Ile Phe Tyr Arg Thr
545 550 555 560
Ile Ile Gly Asn Glu Thr Ala Val Asn Val Asp Ser Ser His Thr Glu
565 570 575
Tyr Thr Leu Ser Ser Leu Thr Ser Asp Thr Leu Tyr Met Val Arg Met
580 585 590
Ala Ala Tyr Thr Asp Glu Gly Gly Lys Asp Gly Pro Glu Phe Arg Ser
595 600 605
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Glu
610 615 620
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
625 630 635 640
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
645 650 655
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
660 665 670
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
675 680 685
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
690 695 700
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
705 710 715 720
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
725 730 735
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
740 745 750
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
755 760 765
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
770 775 780
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
785 790 795 800
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
805 810 815
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
820 825 830
Ser Pro Gly Lys
835
<210> 63
<211> 7711
<212> DNA
<213> artificial sequence
<220>
<223> Matrice TRAC locus_CubiCAR CD22 pCLS30056 full sequence
<400> 63
gtggcacttt tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt 60
caaatatgta tccgctcatg agacaataac cctgataaat gcttcaataa tattgaaaaa 120
ggaagagtat gagtattcaa catttccgtg tcgcccttat tccctttttt gcggcatttt 180
gccttcctgt ttttgctcac ccagaaacgc tggtgaaagt aaaagatgct gaagatcagt 240
tgggtgcacg agtgggttac atcgaactgg atctcaacag cggtaagatc cttgagagtt 300
ttcgccccga agaacgtttt ccaatgatga gcacttttaa agttctgcta tgtggcgcgg 360
tattatcccg tattgacgcc gggcaagagc aactcggtcg ccgcatacac tattctcaga 420
atgacttggt tgagtactca ccagtcacag aaaagcatct tacggatggc atgacagtaa 480
gagaattatg cagtgctgcc ataaccatga gtgataacac tgcggccaac ttacttctga 540
caacgatcgg aggaccgaag gagctaaccg cttttttgca caacatgggg gatcatgtaa 600
ctcgccttga tcgttgggaa ccggagctga atgaagccat accaaacgac gagcgtgaca 660
ccacgatgcc tgtagcaatg gcaacaacgt tgcgcaaact attaactggc gaactactta 720
ctctagcttc ccggcaacaa ttaatagact ggatggaggc ggataaagtt gcaggaccac 780
ttctgcgctc ggcccttccg gctggctggt ttattgctga taaatctgga gccggtgagc 840
gtggttctcg cggtatcatt gcagcactgg ggccagatgg taagccctcc cgtatcgtag 900
ttatctacac gacggggagt caggcaacta tggatgaacg aaatagacag atcgctgaga 960
taggtgcctc actgattaag cattggtaac tgtcagacca agtttactca tatatacttt 1020
agattgattt aaaacttcat ttttaattta aaaggatcta ggtgaagatc ctttttgata 1080
atctcatgac caaaatccct taacgtgagt tttcgttcca ctgagcgtca gaccccgtag 1140
aaaagatcaa aggatcttct tgagatcctt tttttctgcg cgtaatctgc tgcttgcaaa 1200
caaaaaaacc accgctacca gcggtggttt gtttgccgga tcaagagcta ccaactcttt 1260
ttccgaaggt aactggcttc agcagagcgc agataccaaa tactgttctt ctagtgtagc 1320
cgtagttagg ccaccacttc aagaactctg tagcaccgcc tacatacctc gctctgctaa 1380
tcctgttacc agtggctgct gccagtggcg ataagtcgtg tcttaccggg ttggactcaa 1440
gacgatagtt accggataag gcgcagcggt cgggctgaac ggggggttcg tgcacacagc 1500
ccagcttgga gcgaacgacc tacaccgaac tgagatacct acagcgtgag ctatgagaaa 1560
gcgccacgct tcccgaaggg agaaaggcgg acaggtatcc ggtaagcggc agggtcggaa 1620
caggagagcg cacgagggag cttccagggg gaaacgcctg gtatctttat agtcctgtcg 1680
ggtttcgcca cctctgactt gagcgtcgat ttttgtgatg ctcgtcaggg gggcggagcc 1740
tatggaaaaa cgccagcaac gcggcctttt tacggttcct ggccttttgc tggccttttg 1800
ctcacatggt ctttcctgcg ttatcccctg attctgtgga taaccgtatt accgcctttg 1860
agtgagctga taccgctcgc cgcagccgaa cgaccgagcg cagcgagtca gtgagcgagg 1920
aagcggagag cgcccaatac gcaaaccgcc tctccccgcg cgttggccga ttcattaatg 1980
cagctggcac gacaggtttc ccgactggaa agcgggcagt gagcgcaacg caattaatgt 2040
gagttagctc actcattagg caccccaggc tttacacttt atgcttccgg ctcgtatgtt 2100
gtgtggaatt gtgagcggat aacaatttca cacaggaaac agctatgacc atgattacgc 2160
caagcgcgtc aattaaccct cactaaaggg aacaaaagct gttaattaat tgctgggcct 2220
ttttcccatg cctgccttta ctctgccaga gttatattgc tggggttttg aagaagatcc 2280
tattaaataa aagaataagc agtattatta agtagccctg catttcaggt ttccttgagt 2340
ggcaggccag gcctggccgt gaacgttcac tgaaatcatg gcctcttggc caagattgat 2400
agcttgtgcc tgtccctgag tcccagtcca tcacgagcag ctggtttcta agatgctatt 2460
tcccgtataa agcatgagac cgtgacttgc cagccccaca gagccccgcc cttgtccatc 2520
actggcatct ggactccagc ctgggttggg gcaaagaggg aaatgagatc atgtcctaac 2580
cctgatcctc ttgtcccaca gatatccagt acccctacga cgtgcccgac tacgcctccg 2640
gtgagggcag aggaagtctt ctaacatgcg gtgacgtgga ggagaatccg ggccccggat 2700
ccgctctgcc cgtcaccgct ctgctgctgc cactggcact gctgctgcac gctgctaggc 2760
ccggaggggg aggcagctgc ccctacagca accccagcct gtgcagcgga ggcggcggca 2820
gcggcggagg gggtagccag gtgcagctgc agcagagcgg ccctggcctg gtgaagccaa 2880
gccagacact gtccctgacc tgcgccatca gcggcgattc cgtgagctcc aactccgccg 2940
cctggaattg gatcaggcag tccccttctc ggggcctgga gtggctggga aggacatact 3000
atcggtctaa gtggtacaac gattatgccg tgtctgtgaa gagcagaatc acaatcaacc 3060
ctgacacctc caagaatcag ttctctctgc agctgaatag cgtgacacca gaggacaccg 3120
ccgtgtacta ttgcgccagg gaggtgaccg gcgacctgga ggatgccttt gacatctggg 3180
gccagggcac aatggtgacc gtgagctccg gaggcggcgg atctggcgga ggaggaagtg 3240
ggggcggcgg gagtgatatc cagatgacac agtccccatc ctctctgagc gcctccgtgg 3300
gcgacagagt gacaatcacc tgtagggcct cccagaccat ctggtcttac ctgaactggt 3360
atcagcagag gcccggcaag gcccctaatc tgctgatcta cgcagcaagc tccctgcaga 3420
gcggagtgcc atccagattc tctggcaggg gctccggcac agacttcacc ctgaccatct 3480
ctagcctgca ggccgaggac ttcgccacct actattgcca gcagtcttat agcatccccc 3540
agacatttgg ccagggcacc aagctggaga tcaagtcgga tcccggaagc ggagggggag 3600
gcagctgccc ctacagcaac cccagcctgt gcagcggagg cggcggcagc gagctgccca 3660
cccagggcac cttctccaac gtgtccacca acgtgagccc agccaagccc accaccaccg 3720
cctgtcctta ttccaatcct tccctgtgtg ctcccaccac aacccccgct ccaaggcccc 3780
ctacccccgc accaactatt gcctcccagc cactctcact gcggcctgag gcctgtcggc 3840
ccgctgctgg aggcgcagtg catacaaggg gcctcgattt cgcctgcgat atttacatct 3900
gggcacccct cgccggcacc tgcggggtgc ttctcctctc cctggtgatt accctgtatt 3960
gcagacgggg ccggaagaag ctcctctaca tttttaagca gcctttcatg cggccagtgc 4020
agacaaccca agaggaggat gggtgttcct gcagattccc tgaggaagag gaaggcgggt 4080
gcgagctgag agtgaagttc tccaggagcg cagatgcccc cgcctatcaa cagggccaga 4140
accagctcta caacgagctt aacctcggga ggcgcgaaga atacgacgtg ttggataaga 4200
gaagggggcg ggaccccgag atgggaggaa agccccggag gaagaaccct caggagggcc 4260
tgtacaacga gctgcagaag gataagatgg ccgaggccta ctcagagatc gggatgaagg 4320
gggagcggcg ccgcgggaag gggcacgatg ggctctacca ggggctgagc acagccacaa 4380
aggacacata cgacgccttg cacatgcagg cccttccacc ccgggaatag tctagagggc 4440
ccgtttaaac ccgctgatca gcctcgactg tgccttctag ttgccagcca tctgttgttt 4500
gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc ctttcctaat 4560
aaaatgagga aattgcatcg cattgtctga gtaggtgtca ttctattctg gggggtgggg 4620
tggggcagga cagcaagggg gaggattggg aagacaatag caggcatgct ggggatgcgg 4680
tgggctctat gactagtggc gaattcccgt gtaccagctg agagactcta aatccagtga 4740
caagtctgtc tgcctattca ccgattttga ttctcaaaca aatgtgtcac aaagtaagga 4800
ttctgatgtg tatatcacag acaaaactgt gctagacatg aggtctatgg acttcaagag 4860
caacagtgct gtggcctgga gcaacaaatc tgactttgca tgtgcaaacg ccttcaacaa 4920
cagcattatt ccagaagaca ccttcttccc cagcccaggt aagggcagct ttggtgcctt 4980
cgcaggctgt ttccttgctt caggaatggc caggttctgc ccagagctct ggtcaatgat 5040
gtctaaaact cctctgattg gtggtctcgg ccttatccat tgccaccaaa accctctttt 5100
tactaagcga tcgctccggt gcccgtcagt gggcagagcg cacatcgccc acagtccccg 5160
agaagttggg gggaggggtc ggcaattgaa cgggtgccta gagaaggtgg cgcggggtaa 5220
actgggaaag tgatgtcgtg tactggctcc gcctttttcc cgagggtggg ggagaaccgt 5280
atataagtgc agtagtcgcc gtgaacgttc tttttcgcaa cgggtttgcc gccagaacac 5340
agctgaagct tcgaggggct cgcatctctc cttcacgcgc ccgccgccct acctgaggcc 5400
gccatccacg ccggttgagt cgcgttctgc cgcctcccgc ctgtggtgcc tcctgaactg 5460
cgtccgccgt ctaggtaagt ttaaagctca ggtcgagacc gggcctttgt ccggcgctcc 5520
cttggagcct acctagactc agccggctct ccacgctttg cctgaccctg cttgctcaac 5580
tctacgtctt tgtttcgttt tctgttctgc gccgttacag atccaagctg tgaccggcgc 5640
ctacctgaga tcaccggcgc caccatggct tcttaccctg gacaccagca tgcttctgcc 5700
tttgaccagg ctgccagatc caggggccac tccaacagga gaactgccct aagacccaga 5760
agacagcagg aagccactga ggtgaggcct gagcagaaga tgccaaccct gctgagggtg 5820
tacattgatg gacctcatgg catgggcaag accaccacca ctcaactgct ggtggcactg 5880
ggctccaggg atgacattgt gtatgtgcct gagccaatga cctactggag agtgctagga 5940
gcctctgaga ccattgccaa catctacacc acccagcaca ggctggacca gggagaaatc 6000
tctgctggag atgctgctgt ggtgatgacc tctgcccaga tcacaatggg aatgccctat 6060
gctgtgactg atgctgttct ggctcctcac attggaggag aggctggctc ttctcatgcc 6120
cctccacctg ccctgaccct gatctttgac agacacccca ttgcagccct gctgtgctac 6180
ccagcagcaa ggtacctcat gggctccatg accccacagg ctgtgctggc ttttgtggcc 6240
ctgatccctc caaccctccc tggcaccaac attgttctgg gagcactgcc tgaagacaga 6300
cacattgaca ggctggcaaa gaggcagaga cctggagaga gactggacct ggccatgctg 6360
gctgcaatca gaagggtgta tggactgctg gcaaacactg tgagatacct ccagtgtgga 6420
ggctcttgga gagaggactg gggacagctc tctggaacag cagtgccccc tcaaggagct 6480
gagccccagt ccaatgctgg tccaagaccc cacattgggg acaccctgtt caccctgttc 6540
agagcccctg agctgctggc tcccaatgga gacctgtaca atgtgtttgc ctgggctctg 6600
gatgttctag ccaagaggct gaggtccatg catgtgttca tcctggacta tgaccagtcc 6660
cctgctggat gcagagatgc tctgctgcaa ctaacctctg gcatggtgca gacccatgtg 6720
accacccctg gcagcatccc caccatctgt gacctagcca gaacctttgc cagggagatg 6780
ggagaggcca actaaggcgc gccactcgag cgctagctgg ccagacatga taagatacat 6840
tgatgagttt ggacaaacca caactagaat gcagtgaaaa aaatgcttta tttgtgaaat 6900
ttgtgatgct attgctttat ttgtaaccat tataagctgc aataaacaag ttaacaacaa 6960
caattgcatt cattttatgt ttcaggttca gggggaggtg tgggaggttt tttaaagcaa 7020
gtaaaacctc tacaaatgtg gtatggaagg cgcgcccaat tcgccctata gtgagtcgta 7080
ttacgtcgcg ctcactggcc gtcgttttac aacgtcgtga ctgggaaaac cctggcgtta 7140
cccaacttaa tcgccttgca gcacatcccc ctttcgccag ctggcgtaat agcgaagagg 7200
cccgcaccga aacgcccttc ccaacagttg cgcagcctga atggcgaatg ggagcgccct 7260
gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg cagcgtgacc gctacacttg 7320
ccagcgccct agcgcccgct cctttcgctt tcttcccttc ctttctcgcc acgttcgccg 7380
gctttccccg tcaagctcta aatcgggggc tccctttagg gttccgattt agtgctttac 7440
ggcacctcga ccccaaaaaa cttgattagg gtgatggttg gcctgtagtg ggccatagcc 7500
ctgatagacg gtttttcgcc ctttgacgtt ggagtccacg ttctttaata gtggactctt 7560
gttccaaact ggaacaacac tcaaccctat ctcggtctat tcttttgatt tataagggat 7620
tttgccgatt tcggcctatt ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa 7680
ttttaacaaa atattaacgc ttacaattta g 7711
<210> 64
<211> 7502
<212> DNA
<213> artificial sequence
<220>
<223> Matrice CD25 locus_IL15_2A_sIL15Ra pCLS30519 full sequence
<400> 64
gtttattatt cctgttccac agctattgtc tgccatataa aaacttaggc caggcacagt 60
ggctcacacc tgtaatccca gcactttgga aggccgaggc aggcagatca caaggtcagg 120
agttcgagac cagcctggcc aacatagcaa aaccccatct ctactaaaaa tacaaaaatt 180
agccaggcat ggtggcgtgt gcactggttt agagtgagga ccacattttt ttggtgccgt 240
gttacacata tgaccgtgac tttgttacac cactacagga ggaagagtag aagaacaatc 300
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 360
tccaacccag ggcccggtac cgggtccgcc accatggact ggacctggat tctgttcctc 420
gtggctgctg ctacaagagt gcacagcggc attcatgtct tcattttggg ctgtttcagt 480
gcagggcttc ctaaaacaga agccaactgg gtgaatgtaa taagtgattt gaaaaaaatt 540
gaagatctta ttcaatctat gcatattgat gctactttat atacggaaag tgatgttcac 600
cccagttgca aagtaacagc aatgaagtgc tttctcttgg agttacaagt tatttcactt 660
gagtccggag atgcaagtat tcatgataca gtagaaaatc tgatcatcct agcaaacaac 720
agtttgtctt ctaatgggaa tgtaacagaa tctggatgca aagaatgtga ggaactggag 780
gaaaaaaata ttaaagaatt tttgcagagt tttgtacata ttgtccaaat gttcatcaac 840
acttctggaa gcggagctac taacttcagc ctgctgaagc aggctggaga cgtggaggag 900
aaccctggac ctgggaccgg ctctgcaacc atggattgga cgtggatcct gtttctcgtg 960
gcagctgcca caagagttca cagtatcacg tgccctcccc ccatgtccgt ggaacacgca 1020
gacatctggg tcaagagcta cagcttgtac tccagggagc ggtacatttg taactctggt 1080
ttcaagcgta aagccggcac gtccagcctg acggagtgcg tgttgaacaa ggccacgaat 1140
gtcgcccact ggacaacccc cagtctcaaa tgcattagag accctgccct ggttcaccaa 1200
aggccagcgc caccctccac agtaacgacg gcaggggtga ccccacagcc agagagcctc 1260
tccccttctg gaaaagagcc cgcagcttca tctcccagct caaacaacac agcggccaca 1320
acagcagcta ttgtcccggg ctcccagctg atgccttcaa aatcaccttc cacaggaacc 1380
acagagataa gcagtcatga gtcctcccac ggcaccccct ctcagacaac agccaagaac 1440
tgggaactca cagcatccgc ctcccaccag ccgccaggtg tgtatccaca gggccacagc 1500
gacaccactg agggcagagg cagcctgctg acctgcggcg acgtcgagga gaaccccggg 1560
cccatggggg caggtgccac cggccgcgcc atggacgggc cgcgcctgct gctgttgctg 1620
cttctggggg tgtcccttgg aggtgccaag gaggcatgcc ccacaggcct gtacacacac 1680
agcggtgagt gctgcaaagc ctgcaacctg ggcgagggtg tggcccagcc ttgtggagcc 1740
aaccagaccg tgtgtgagcc ctgcctggac agcgtgacgt tctccgacgt ggtgagcgcg 1800
accgagccgt gcaagccgtg caccgagtgc gtggggctcc agagcatgtc ggcgccgtgc 1860
gtggaggccg atgacgccgt gtgccgctgc gcctacggct actaccagga tgagacgact 1920
gggcgctgcg aggcgtgccg cgtgtgcgag gcgggctcgg gcctcgtgtt ctcctgccag 1980
gacaagcaga acaccgtgtg cgaggagtgc cccgacggca cgtattccga cgaggccaac 2040
cacgtggacc cgtgcctgcc ctgcaccgtg tgcgaggaca ccgagcgcca gctccgcgag 2100
tgcacacgct gggccgacgc cgagtgcgag gagatccctg gccgttggat tacacggtcc 2160
acacccccag agggctcgga cagcacagcc cccagcaccc aggagcctga ggcacctcca 2220
gaacaagacc tcatagccag cacggtggca ggtgtggtga ccacagtgat gggcagctcc 2280
cagcccgtgg tgacccgagg caccaccgac aacctcatcc ctgtctattg ctccatcctg 2340
gctgctgtgg ttgtgggtct tgtggcctac atagccttca agaggtgaaa aaccaaaaga 2400
acaagaattt cttggtaaga agccgggaac agacaacaga agtcatgaag cccaagtgaa 2460
atcaaaggtg ctaaatggtc gcccaggaga catccgttgt gcttgcctgc gttttggaag 2520
ctctgaagtc acatcacagg acacggggca gtggcaacct tgtctctatg ccagctcagt 2580
cccatcagag agcgagcgct acccacttct aaatagcaat ttcgccgttg aagaggaagg 2640
gcaaaaccac tagaactctc catcttattt tcatgtatat gtgttcatgc gatcgctccg 2700
gtgcccgtca gtgggcagag cgcacatcgc ccacagtccc cgagaagttg gggggagggg 2760
tcggcaattg aacgggtgcc tagagaaggt ggcgcggggt aaactgggaa agtgatgtcg 2820
tgtactggct ccgccttttt cccgagggtg ggggagaacc gtatataagt gcagtagtcg 2880
ccgtgaacgt tctttttcgc aacgggtttg ccgccagaac acagctgaag cttcgagggg 2940
ctcgcatctc tccttcacgc gcccgccgcc ctacctgagg ccgccatcca cgccggttga 3000
gtcgcgttct gccgcctccc gcctgtggtg cctcctgaac tgcgtccgcc gtctaggtaa 3060
gtttaaagct caggtcgaga ccgggccttt gtccggcgct cccttggagc ctacctagac 3120
tcagccggct ctccacgctt tgcctgaccc tgcttgctca actctacgtc tttgtttcgt 3180
tttctgttct gcgccgttac agatccaagc tgtgaccggc gcctacctga gatcaccggc 3240
gccaccatgg cttcttaccc tggacaccag catgcttctg cctttgacca ggctgccaga 3300
tccaggggcc actccaacag gagaactgcc ctaagaccca gaagacagca ggaagccact 3360
gaggtgaggc ctgagcagaa gatgccaacc ctgctgaggg tgtacattga tggacctcat 3420
ggcatgggca agaccaccac cactcaactg ctggtggcac tgggctccag ggatgacatt 3480
gtgtatgtgc ctgagccaat gacctactgg agagtgctag gagcctctga gaccattgcc 3540
aacatctaca ccacccagca caggctggac cagggagaaa tctctgctgg agatgctgct 3600
gtggtgatga cctctgccca gatcacaatg ggaatgccct atgctgtgac tgatgctgtt 3660
ctggctcctc acattggagg agaggctggc tcttctcatg cccctccacc tgccctgacc 3720
ctgatctttg acagacaccc cattgcagcc ctgctgtgct acccagcagc aaggtacctc 3780
atgggctcca tgaccccaca ggctgtgctg gcttttgtgg ccctgatccc tccaaccctc 3840
cctggcacca acattgttct gggagcactg cctgaagaca gacacattga caggctggca 3900
aagaggcaga gacctggaga gagactggac ctggccatgc tggctgcaat cagaagggtg 3960
tatggactgc tggcaaacac tgtgagatac ctccagtgtg gaggctcttg gagagaggac 4020
tggggacagc tctctggaac agcagtgccc cctcaaggag ctgagcccca gtccaatgct 4080
ggtccaagac cccacattgg ggacaccctg ttcaccctgt tcagagcccc tgagctgctg 4140
gctcccaatg gagacctgta caatgtgttt gcctgggctc tggatgttct agccaagagg 4200
ctgaggtcca tgcatgtgtt catcctggac tatgaccagt cccctgctgg atgcagagat 4260
gctctgctgc aactaacctc tggcatggtg cagacccatg tgaccacccc tggcagcatc 4320
cccaccatct gtgacctagc cagaaccttt gccagggaga tgggagaggc caactaaggc 4380
gcgccactcg agcgctagct ggccagacat gataagatac attgatgagt ttggacaaac 4440
cacaactaga atgcagtgaa aaaaatgctt tatttgtgaa atttgtgatg ctattgcttt 4500
atttgtaacc attataagct gcaataaaca agttaacaac aacaattgca ttcattttat 4560
gtttcaggtt cagggggagg tgtgggaggt tttttaaagc aagtaaaacc tctacaaatg 4620
tggtatggaa ggcgcgccca attcgcccta tagtgagtcg tattacgtcg cgctcactgg 4680
ccgtcgtttt acaacgtcgt gactgggaaa accctggcgt tacccaactt aatcgccttg 4740
cagcacatcc ccctttcgcc agctggcgta atagcgaaga ggcccgcacc gaaacgccct 4800
tcccaacagt tgcgcagcct gaatggcgaa tgggagcgcc ctgtagcggc gcattaagcg 4860
cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc ctagcgcccg 4920
ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc cgtcaagctc 4980
taaatcgggg gctcccttta gggttccgat ttagtgcttt acggcacctc gaccccaaaa 5040
aacttgatta gggtgatggt tggcctgtag tgggccatag ccctgataga cggtttttcg 5100
ccctttgacg ttggagtcca cgttctttaa tagtggactc ttgttccaaa ctggaacaac 5160
actcaaccct atctcggtct attcttttga tttataaggg attttgccga tttcggccta 5220
ttggttaaaa aatgagctga tttaacaaaa atttaacgcg aattttaaca aaatattaac 5280
gcttacaatt taggtggcac ttttcgggga aatgtgcgcg gaacccctat ttgtttattt 5340
ttctaaatac attcaaatat gtatccgctc atgagacaat aaccctgata aatgcttcaa 5400
taatattgaa aaaggaagag tatgagtatt caacatttcc gtgtcgccct tattcccttt 5460
tttgcggcat tttgccttcc tgtttttgct cacccagaaa cgctggtgaa agtaaaagat 5520
gctgaagatc agttgggtgc acgagtgggt tacatcgaac tggatctcaa cagcggtaag 5580
atccttgaga gttttcgccc cgaagaacgt tttccaatga tgagcacttt taaagttctg 5640
ctatgtggcg cggtattatc ccgtattgac gccgggcaag agcaactcgg tcgccgcata 5700
cactattctc agaatgactt ggttgagtac tcaccagtca cagaaaagca tcttacggat 5760
ggcatgacag taagagaatt atgcagtgct gccataacca tgagtgataa cactgcggcc 5820
aacttacttc tgacaacgat cggaggaccg aaggagctaa ccgctttttt gcacaacatg 5880
ggggatcatg taactcgcct tgatcgttgg gaaccggagc tgaatgaagc cataccaaac 5940
gacgagcgtg acaccacgat gcctgtagca atggcaacaa cgttgcgcaa actattaact 6000
ggcgaactac ttactctagc ttcccggcaa caattaatag actggatgga ggcggataaa 6060
gttgcaggac cacttctgcg ctcggccctt ccggctggct ggtttattgc tgataaatct 6120
ggagccggtg agcgtggttc tcgcggtatc attgcagcac tggggccaga tggtaagccc 6180
tcccgtatcg tagttatcta cacgacgggg agtcaggcaa ctatggatga acgaaataga 6240
cagatcgctg agataggtgc ctcactgatt aagcattggt aactgtcaga ccaagtttac 6300
tcatatatac tttagattga tttaaaactt catttttaat ttaaaaggat ctaggtgaag 6360
atcctttttg ataatctcat gaccaaaatc ccttaacgtg agttttcgtt ccactgagcg 6420
tcagaccccg tagaaaagat caaaggatct tcttgagatc ctttttttct gcgcgtaatc 6480
tgctgcttgc aaacaaaaaa accaccgcta ccagcggtgg tttgtttgcc ggatcaagag 6540
ctaccaactc tttttccgaa ggtaactggc ttcagcagag cgcagatacc aaatactgtt 6600
cttctagtgt agccgtagtt aggccaccac ttcaagaact ctgtagcacc gcctacatac 6660
ctcgctctgc taatcctgtt accagtggct gctgccagtg gcgataagtc gtgtcttacc 6720
gggttggact caagacgata gttaccggat aaggcgcagc ggtcgggctg aacggggggt 6780
tcgtgcacac agcccagctt ggagcgaacg acctacaccg aactgagata cctacagcgt 6840
gagctatgag aaagcgccac gcttcccgaa gggagaaagg cggacaggta tccggtaagc 6900
ggcagggtcg gaacaggaga gcgcacgagg gagcttccag ggggaaacgc ctggtatctt 6960
tatagtcctg tcgggtttcg ccacctctga cttgagcgtc gatttttgtg atgctcgtca 7020
ggggggcgga gcctatggaa aaacgccagc aacgcggcct ttttacggtt cctggccttt 7080
tgctggcctt ttgctcacat ggtctttcct gcgttatccc ctgattctgt ggataaccgt 7140
attaccgcct ttgagtgagc tgataccgct cgccgcagcc gaacgaccga gcgcagcgag 7200
tcagtgagcg aggaagcgga gagcgcccaa tacgcaaacc gcctctcccc gcgcgttggc 7260
cgattcatta atgcagctgg cacgacaggt ttcccgactg gaaagcgggc agtgagcgca 7320
acgcaattaa tgtgagttag ctcactcatt aggcacccca ggctttacac tttatgcttc 7380
cggctcgtat gttgtgtgga attgtgagcg gataacaatt tcacacagga aacagctatg 7440
accatgatta cgccaagcgc gtcaattaac cctcactaaa gggaacaaaa gctgttaatt 7500
aa 7502
<210> 65
<211> 7778
<212> DNA
<213> artificial sequence
<220>
<223> Matrice PD1 locus_IL15_2A_sIL15Ra pCLS30513 full sequence
<400> 65
gactccccag acaggccctg gaaccccccc accttctccc cagccctgct cgtggtgacc 60
gaaggggaca acgccacctt cacctgcagc ttctccaaca catcggagag cttcgtgcta 120
aactggtacc gcatgagccc cagcaaccag acggacaagc tggccgcctt ccccgaggac 180
cgcagccagc ccggccagga ctgccgcttc cgtgtcacac aactgcccaa cgggcgtgac 240
ttccacatga gcgtggtcag ggcccggcgc aatgacagcg gcacctacct ctgtggggcc 300
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 360
tccaacccag ggcccggtac cgggtccgcc accatggact ggacctggat tctgttcctc 420
gtggctgctg ctacaagagt gcacagcggc attcatgtct tcattttggg ctgtttcagt 480
gcagggcttc ctaaaacaga agccaactgg gtgaatgtaa taagtgattt gaaaaaaatt 540
gaagatctta ttcaatctat gcatattgat gctactttat atacggaaag tgatgttcac 600
cccagttgca aagtaacagc aatgaagtgc tttctcttgg agttacaagt tatttcactt 660
gagtccggag atgcaagtat tcatgataca gtagaaaatc tgatcatcct agcaaacaac 720
agtttgtctt ctaatgggaa tgtaacagaa tctggatgca aagaatgtga ggaactggag 780
gaaaaaaata ttaaagaatt tttgcagagt tttgtacata ttgtccaaat gttcatcaac 840
acttctggaa gcggagctac taacttcagc ctgctgaagc aggctggaga cgtggaggag 900
aaccctggac ctgggaccgg ctctgcaacc atggattgga cgtggatcct gtttctcgtg 960
gcagctgcca caagagttca cagtatcacg tgccctcccc ccatgtccgt ggaacacgca 1020
gacatctggg tcaagagcta cagcttgtac tccagggagc ggtacatttg taactctggt 1080
ttcaagcgta aagccggcac gtccagcctg acggagtgcg tgttgaacaa ggccacgaat 1140
gtcgcccact ggacaacccc cagtctcaaa tgcattagag accctgccct ggttcaccaa 1200
aggccagcgc caccctccac agtaacgacg gcaggggtga ccccacagcc agagagcctc 1260
tccccttctg gaaaagagcc cgcagcttca tctcccagct caaacaacac agcggccaca 1320
acagcagcta ttgtcccggg ctcccagctg atgccttcaa aatcaccttc cacaggaacc 1380
acagagataa gcagtcatga gtcctcccac ggcaccccct ctcagacaac agccaagaac 1440
tgggaactca cagcatccgc ctcccaccag ccgccaggtg tgtatccaca gggccacagc 1500
gacaccactg agggcagagg cagcctgctg acctgcggcg acgtcgagga gaaccccggg 1560
cccatggggg caggtgccac cggccgcgcc atggacgggc cgcgcctgct gctgttgctg 1620
cttctggggg tgtcccttgg aggtgccaag gaggcatgcc ccacaggcct gtacacacac 1680
agcggtgagt gctgcaaagc ctgcaacctg ggcgagggtg tggcccagcc ttgtggagcc 1740
aaccagaccg tgtgtgagcc ctgcctggac agcgtgacgt tctccgacgt ggtgagcgcg 1800
accgagccgt gcaagccgtg caccgagtgc gtggggctcc agagcatgtc ggcgccgtgc 1860
gtggaggccg atgacgccgt gtgccgctgc gcctacggct actaccagga tgagacgact 1920
gggcgctgcg aggcgtgccg cgtgtgcgag gcgggctcgg gcctcgtgtt ctcctgccag 1980
gacaagcaga acaccgtgtg cgaggagtgc cccgacggca cgtattccga cgaggccaac 2040
cacgtggacc cgtgcctgcc ctgcaccgtg tgcgaggaca ccgagcgcca gctccgcgag 2100
tgcacacgct gggccgacgc cgagtgcgag gagatccctg gccgttggat tacacggtcc 2160
acacccccag agggctcgga cagcacagcc cccagcaccc aggagcctga ggcacctcca 2220
gaacaagacc tcatagccag cacggtggca ggtgtggtga ccacagtgat gggcagctcc 2280
cagcccgtgg tgacccgagg caccaccgac aacctcatcc ctgtctattg ctccatcctg 2340
gctgctgtgg ttgtgggtct tgtggcctac atagccttca agaggtgatc tagagggccc 2400
gtttaaaccc gctgatcagc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc 2460
ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa 2520
aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg 2580
gggcaggaca gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg 2640
ggctctatga ctagtggcga attcggcgca gatcaaagag agcctgcggg cagagctcag 2700
ggtgacaggt gcggcctcgg aggccccggg gcaggggtga gctgagccgg tcctggggtg 2760
ggtgtcccct cctgcacagg atcaggagct ccagggtcgt agggcaggga ccccccagct 2820
ccagtccagg gctctgtcct gcacctgggg aatggtgacc ggcatctctg tcctctagct 2880
ctggaagcac cccagcccct ctagtctgcc ctcacccctg accctgaccc tccaccctga 2940
ccccgtccta acccctgacc tttggcgatc gctccggtgc ccgtcagtgg gcagagcgca 3000
catcgcccac agtccccgag aagttggggg gaggggtcgg caattgaacg ggtgcctaga 3060
gaaggtggcg cggggtaaac tgggaaagtg atgtcgtgta ctggctccgc ctttttcccg 3120
agggtggggg agaaccgtat ataagtgcag tagtcgccgt gaacgttctt tttcgcaacg 3180
ggtttgccgc cagaacacag ctgaagcttc gaggggctcg catctctcct tcacgcgccc 3240
gccgccctac ctgaggccgc catccacgcc ggttgagtcg cgttctgccg cctcccgcct 3300
gtggtgcctc ctgaactgcg tccgccgtct aggtaagttt aaagctcagg tcgagaccgg 3360
gcctttgtcc ggcgctccct tggagcctac ctagactcag ccggctctcc acgctttgcc 3420
tgaccctgct tgctcaactc tacgtctttg tttcgttttc tgttctgcgc cgttacagat 3480
ccaagctgtg accggcgcct acctgagatc accggcgcca ccatggcttc ttaccctgga 3540
caccagcatg cttctgcctt tgaccaggct gccagatcca ggggccactc caacaggaga 3600
actgccctaa gacccagaag acagcaggaa gccactgagg tgaggcctga gcagaagatg 3660
ccaaccctgc tgagggtgta cattgatgga cctcatggca tgggcaagac caccaccact 3720
caactgctgg tggcactggg ctccagggat gacattgtgt atgtgcctga gccaatgacc 3780
tactggagag tgctaggagc ctctgagacc attgccaaca tctacaccac ccagcacagg 3840
ctggaccagg gagaaatctc tgctggagat gctgctgtgg tgatgacctc tgcccagatc 3900
acaatgggaa tgccctatgc tgtgactgat gctgttctgg ctcctcacat tggaggagag 3960
gctggctctt ctcatgcccc tccacctgcc ctgaccctga tctttgacag acaccccatt 4020
gcagccctgc tgtgctaccc agcagcaagg tacctcatgg gctccatgac cccacaggct 4080
gtgctggctt ttgtggccct gatccctcca accctccctg gcaccaacat tgttctggga 4140
gcactgcctg aagacagaca cattgacagg ctggcaaaga ggcagagacc tggagagaga 4200
ctggacctgg ccatgctggc tgcaatcaga agggtgtatg gactgctggc aaacactgtg 4260
agatacctcc agtgtggagg ctcttggaga gaggactggg gacagctctc tggaacagca 4320
gtgccccctc aaggagctga gccccagtcc aatgctggtc caagacccca cattggggac 4380
accctgttca ccctgttcag agcccctgag ctgctggctc ccaatggaga cctgtacaat 4440
gtgtttgcct gggctctgga tgttctagcc aagaggctga ggtccatgca tgtgttcatc 4500
ctggactatg accagtcccc tgctggatgc agagatgctc tgctgcaact aacctctggc 4560
atggtgcaga cccatgtgac cacccctggc agcatcccca ccatctgtga cctagccaga 4620
acctttgcca gggagatggg agaggccaac taaggcgcgc cactcgagcg ctagctggcc 4680
agacatgata agatacattg atgagtttgg acaaaccaca actagaatgc agtgaaaaaa 4740
atgctttatt tgtgaaattt gtgatgctat tgctttattt gtaaccatta taagctgcaa 4800
taaacaagtt aacaacaaca attgcattca ttttatgttt caggttcagg gggaggtgtg 4860
ggaggttttt taaagcaagt aaaacctcta caaatgtggt atggaaggcg cgcccaattc 4920
gccctatagt gagtcgtatt acgtcgcgct cactggccgt cgttttacaa cgtcgtgact 4980
gggaaaaccc tggcgttacc caacttaatc gccttgcagc acatccccct ttcgccagct 5040
ggcgtaatag cgaagaggcc cgcaccgaaa cgcccttccc aacagttgcg cagcctgaat 5100
ggcgaatggg agcgccctgt agcggcgcat taagcgcggc gggtgtggtg gttacgcgca 5160
gcgtgaccgc tacacttgcc agcgccctag cgcccgctcc tttcgctttc ttcccttcct 5220
ttctcgccac gttcgccggc tttccccgtc aagctctaaa tcgggggctc cctttagggt 5280
tccgatttag tgctttacgg cacctcgacc ccaaaaaact tgattagggt gatggttggc 5340
ctgtagtggg ccatagccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 5400
ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 5460
ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 5520
acaaaaattt aacgcgaatt ttaacaaaat attaacgctt acaatttagg tggcactttt 5580
cggggaaatg tgcgcggaac ccctatttgt ttatttttct aaatacattc aaatatgtat 5640
ccgctcatga gacaataacc ctgataaatg cttcaataat attgaaaaag gaagagtatg 5700
agtattcaac atttccgtgt cgcccttatt cccttttttg cggcattttg ccttcctgtt 5760
tttgctcacc cagaaacgct ggtgaaagta aaagatgctg aagatcagtt gggtgcacga 5820
gtgggttaca tcgaactgga tctcaacagc ggtaagatcc ttgagagttt tcgccccgaa 5880
gaacgttttc caatgatgag cacttttaaa gttctgctat gtggcgcggt attatcccgt 5940
attgacgccg ggcaagagca actcggtcgc cgcatacact attctcagaa tgacttggtt 6000
gagtactcac cagtcacaga aaagcatctt acggatggca tgacagtaag agaattatgc 6060
agtgctgcca taaccatgag tgataacact gcggccaact tacttctgac aacgatcgga 6120
ggaccgaagg agctaaccgc ttttttgcac aacatggggg atcatgtaac tcgccttgat 6180
cgttgggaac cggagctgaa tgaagccata ccaaacgacg agcgtgacac cacgatgcct 6240
gtagcaatgg caacaacgtt gcgcaaacta ttaactggcg aactacttac tctagcttcc 6300
cggcaacaat taatagactg gatggaggcg gataaagttg caggaccact tctgcgctcg 6360
gcccttccgg ctggctggtt tattgctgat aaatctggag ccggtgagcg tggttctcgc 6420
ggtatcattg cagcactggg gccagatggt aagccctccc gtatcgtagt tatctacacg 6480
acggggagtc aggcaactat ggatgaacga aatagacaga tcgctgagat aggtgcctca 6540
ctgattaagc attggtaact gtcagaccaa gtttactcat atatacttta gattgattta 6600
aaacttcatt tttaatttaa aaggatctag gtgaagatcc tttttgataa tctcatgacc 6660
aaaatccctt aacgtgagtt ttcgttccac tgagcgtcag accccgtaga aaagatcaaa 6720
ggatcttctt gagatccttt ttttctgcgc gtaatctgct gcttgcaaac aaaaaaacca 6780
ccgctaccag cggtggtttg tttgccggat caagagctac caactctttt tccgaaggta 6840
actggcttca gcagagcgca gataccaaat actgttcttc tagtgtagcc gtagttaggc 6900
caccacttca agaactctgt agcaccgcct acatacctcg ctctgctaat cctgttacca 6960
gtggctgctg ccagtggcga taagtcgtgt cttaccgggt tggactcaag acgatagtta 7020
ccggataagg cgcagcggtc gggctgaacg gggggttcgt gcacacagcc cagcttggag 7080
cgaacgacct acaccgaact gagataccta cagcgtgagc tatgagaaag cgccacgctt 7140
cccgaaggga gaaaggcgga caggtatccg gtaagcggca gggtcggaac aggagagcgc 7200
acgagggagc ttccaggggg aaacgcctgg tatctttata gtcctgtcgg gtttcgccac 7260
ctctgacttg agcgtcgatt tttgtgatgc tcgtcagggg ggcggagcct atggaaaaac 7320
gccagcaacg cggccttttt acggttcctg gccttttgct ggccttttgc tcacatggtc 7380
tttcctgcgt tatcccctga ttctgtggat aaccgtatta ccgcctttga gtgagctgat 7440
accgctcgcc gcagccgaac gaccgagcgc agcgagtcag tgagcgagga agcggagagc 7500
gcccaatacg caaaccgcct ctccccgcgc gttggccgat tcattaatgc agctggcacg 7560
acaggtttcc cgactggaaa gcgggcagtg agcgcaacgc aattaatgtg agttagctca 7620
ctcattaggc accccaggct ttacacttta tgcttccggc tcgtatgttg tgtggaattg 7680
tgagcggata acaatttcac acaggaaaca gctatgacca tgattacgcc aagcgcgtca 7740
attaaccctc actaaaggga acaaaagctg ttaattaa 7778
<210> 66
<211> 8177
<212> DNA
<213> artificial sequence
<220>
<223> Matrice CD25 locus_IL12a_2A_IL12b pCLS30520 full sequence
<400> 66
gtttattatt cctgttccac agctattgtc tgccatataa aaacttaggc caggcacagt 60
ggctcacacc tgtaatccca gcactttgga aggccgaggc aggcagatca caaggtcagg 120
agttcgagac cagcctggcc aacatagcaa aaccccatct ctactaaaaa tacaaaaatt 180
agccaggcat ggtggcgtgt gcactggttt agagtgagga ccacattttt ttggtgccgt 240
gttacacata tgaccgtgac tttgttacac cactacagga ggaagagtag aagaacaatc 300
ggttctggcg tgaaacagac tttgaatttt gaccttctca agttggcggg agacgtggag 360
tccaacccag ggcccatgtg gccccctggg tcagcctccc agccaccgcc ctcacctgcc 420
gcggccacag gtctgcatcc agcggctcgc cctgtgtccc tgcagtgccg gctcagcatg 480
tgtccagcgc gcagcctcct ccttgtggct accctggtcc tcctggacca cctcagtttg 540
gccagaaacc tccccgtggc cactccagac ccaggaatgt tcccatgcct tcaccactcc 600
caaaacctgc tgagggccgt cagcaacatg ctccagaagg ccagacaaac tctagaattt 660
tacccttgca cttctgaaga gattgatcat gaagatatca caaaagataa aaccagcaca 720
gtggaggcct gtttaccatt ggaattaacc aagaatgaga gttgcctaaa ttccagagag 780
acctctttca taactaatgg gagttgcctg gcctccagaa agacctcttt tatgatggcc 840
ctgtgcctta gtagtattta tgaagacttg aagatgtacc aggtggagtt caagaccatg 900
aatgcaaagc ttctgatgga tcctaagagg cagatctttc tagatcaaaa catgctggca 960
gttattgatg agctgatgca ggccctgaat ttcaacagtg agactgtgcc acaaaaatcc 1020
tcccttgaag aaccggattt ttataaaact aaaatcaagc tctgcatact tcttcatgct 1080
ttcagaattc gggcagtgac tattgataga gtgatgagct atctgaatgc ttccggaagc 1140
ggagctacta acttcagcct gctgaagcag gctggagacg tggaggagaa ccctggacct 1200
atgtgtcacc agcagttggt catctcttgg ttttccctgg tttttctggc atctcccctc 1260
gtggccatat gggaactgaa gaaagatgtt tatgtcgtag aattggattg gtatccggat 1320
gcccctggag aaatggtggt cctcacctgt gacacccctg aagaagatgg tatcacctgg 1380
accttggacc agagcagtga ggtcttaggc tctggcaaaa ccctgaccat ccaagtcaaa 1440
gagtttggag atgctggcca gtacacctgt cacaaaggag gcgaggttct aagccattcg 1500
ctcctgctgc ttcacaaaaa ggaagatgga atttggtcca ctgatatttt aaaggaccag 1560
aaagaaccca aaaataagac ctttctaaga tgcgaggcca agaattattc tggacgtttc 1620
acctgctggt ggctgacgac aatcagtact gatttgacat tcagtgtcaa aagcagcaga 1680
ggctcttctg acccccaagg ggtgacgtgc ggagctgcta cactctctgc agagagagtc 1740
agaggggaca acaaggagta tgagtactca gtggagtgcc aggaggacag tgcctgccca 1800
gctgctgagg agagtctgcc cattgaggtc atggtggatg ccgttcacaa gctcaagtat 1860
gaaaactaca ccagcagctt cttcatcagg gacatcatca aacctgaccc acccaagaac 1920
ttgcagctga agccattaaa gaattctcgg caggtggagg tcagctggga gtaccctgac 1980
acctggagta ctccacattc ctacttctcc ctgacattct gcgttcaggt ccagggcaag 2040
agcaagagag aaaagaaaga tagagtcttc acggacaaga cctcagccac ggtcatctgc 2100
cgcaaaaatg ccagcattag cgtgcgggcc caggaccgct actatagctc atcttggagc 2160
gaatgggcat ctgtgccctg cagtgagggc agaggcagcc tgctgacctg cggcgacgtc 2220
gaggagaacc ccgggcccat gggggcaggt gccaccggcc gcgccatgga cgggccgcgc 2280
ctgctgctgt tgctgcttct gggggtgtcc cttggaggtg ccaaggaggc atgccccaca 2340
ggcctgtaca cacacagcgg tgagtgctgc aaagcctgca acctgggcga gggtgtggcc 2400
cagccttgtg gagccaacca gaccgtgtgt gagccctgcc tggacagcgt gacgttctcc 2460
gacgtggtga gcgcgaccga gccgtgcaag ccgtgcaccg agtgcgtggg gctccagagc 2520
atgtcggcgc cgtgcgtgga ggccgatgac gccgtgtgcc gctgcgccta cggctactac 2580
caggatgaga cgactgggcg ctgcgaggcg tgccgcgtgt gcgaggcggg ctcgggcctc 2640
gtgttctcct gccaggacaa gcagaacacc gtgtgcgagg agtgccccga cggcacgtat 2700
tccgacgagg ccaaccacgt ggacccgtgc ctgccctgca ccgtgtgcga ggacaccgag 2760
cgccagctcc gcgagtgcac acgctgggcc gacgccgagt gcgaggagat ccctggccgt 2820
tggattacac ggtccacacc cccagagggc tcggacagca cagcccccag cacccaggag 2880
cctgaggcac ctccagaaca agacctcata gccagcacgg tggcaggtgt ggtgaccaca 2940
gtgatgggca gctcccagcc cgtggtgacc cgaggcacca ccgacaacct catccctgtc 3000
tattgctcca tcctggctgc tgtggttgtg ggtcttgtgg cctacatagc cttcaagagg 3060
tgaaaaacca aaagaacaag aatttcttgg taagaagccg ggaacagaca acagaagtca 3120
tgaagcccaa gtgaaatcaa aggtgctaaa tggtcgccca ggagacatcc gttgtgcttg 3180
cctgcgtttt ggaagctctg aagtcacatc acaggacacg gggcagtggc aaccttgtct 3240
ctatgccagc tcagtcccat cagagagcga gcgctaccca cttctaaata gcaatttcgc 3300
cgttgaagag gaagggcaaa accactagaa ctctccatct tattttcatg tatatgtgtt 3360
catgcgatcg ctccggtgcc cgtcagtggg cagagcgcac atcgcccaca gtccccgaga 3420
agttgggggg aggggtcggc aattgaacgg gtgcctagag aaggtggcgc ggggtaaact 3480
gggaaagtga tgtcgtgtac tggctccgcc tttttcccga gggtggggga gaaccgtata 3540
taagtgcagt agtcgccgtg aacgttcttt ttcgcaacgg gtttgccgcc agaacacagc 3600
tgaagcttcg aggggctcgc atctctcctt cacgcgcccg ccgccctacc tgaggccgcc 3660
atccacgccg gttgagtcgc gttctgccgc ctcccgcctg tggtgcctcc tgaactgcgt 3720
ccgccgtcta ggtaagttta aagctcaggt cgagaccggg cctttgtccg gcgctccctt 3780
ggagcctacc tagactcagc cggctctcca cgctttgcct gaccctgctt gctcaactct 3840
acgtctttgt ttcgttttct gttctgcgcc gttacagatc caagctgtga ccggcgccta 3900
cctgagatca ccggcgccac catggcttct taccctggac accagcatgc ttctgccttt 3960
gaccaggctg ccagatccag gggccactcc aacaggagaa ctgccctaag acccagaaga 4020
cagcaggaag ccactgaggt gaggcctgag cagaagatgc caaccctgct gagggtgtac 4080
attgatggac ctcatggcat gggcaagacc accaccactc aactgctggt ggcactgggc 4140
tccagggatg acattgtgta tgtgcctgag ccaatgacct actggagagt gctaggagcc 4200
tctgagacca ttgccaacat ctacaccacc cagcacaggc tggaccaggg agaaatctct 4260
gctggagatg ctgctgtggt gatgacctct gcccagatca caatgggaat gccctatgct 4320
gtgactgatg ctgttctggc tcctcacatt ggaggagagg ctggctcttc tcatgcccct 4380
ccacctgccc tgaccctgat ctttgacaga caccccattg cagccctgct gtgctaccca 4440
gcagcaaggt acctcatggg ctccatgacc ccacaggctg tgctggcttt tgtggccctg 4500
atccctccaa ccctccctgg caccaacatt gttctgggag cactgcctga agacagacac 4560
attgacaggc tggcaaagag gcagagacct ggagagagac tggacctggc catgctggct 4620
gcaatcagaa gggtgtatgg actgctggca aacactgtga gatacctcca gtgtggaggc 4680
tcttggagag aggactgggg acagctctct ggaacagcag tgccccctca aggagctgag 4740
ccccagtcca atgctggtcc aagaccccac attggggaca ccctgttcac cctgttcaga 4800
gcccctgagc tgctggctcc caatggagac ctgtacaatg tgtttgcctg ggctctggat 4860
gttctagcca agaggctgag gtccatgcat gtgttcatcc tggactatga ccagtcccct 4920
gctggatgca gagatgctct gctgcaacta acctctggca tggtgcagac ccatgtgacc 4980
acccctggca gcatccccac catctgtgac ctagccagaa cctttgccag ggagatggga 5040
gaggccaact aaggcgcgcc actcgagcgc tagctggcca gacatgataa gatacattga 5100
tgagtttgga caaaccacaa ctagaatgca gtgaaaaaaa tgctttattt gtgaaatttg 5160
tgatgctatt gctttatttg taaccattat aagctgcaat aaacaagtta acaacaacaa 5220
ttgcattcat tttatgtttc aggttcaggg ggaggtgtgg gaggtttttt aaagcaagta 5280
aaacctctac aaatgtggta tggaaggcgc gcccaattcg ccctatagtg agtcgtatta 5340
cgtcgcgctc actggccgtc gttttacaac gtcgtgactg ggaaaaccct ggcgttaccc 5400
aacttaatcg ccttgcagca catccccctt tcgccagctg gcgtaatagc gaagaggccc 5460
gcaccgaaac gcccttccca acagttgcgc agcctgaatg gcgaatggga gcgccctgta 5520
gcggcgcatt aagcgcggcg ggtgtggtgg ttacgcgcag cgtgaccgct acacttgcca 5580
gcgccctagc gcccgctcct ttcgctttct tcccttcctt tctcgccacg ttcgccggct 5640
ttccccgtca agctctaaat cgggggctcc ctttagggtt ccgatttagt gctttacggc 5700
acctcgaccc caaaaaactt gattagggtg atggttggcc tgtagtgggc catagccctg 5760
atagacggtt tttcgccctt tgacgttgga gtccacgttc tttaatagtg gactcttgtt 5820
ccaaactgga acaacactca accctatctc ggtctattct tttgatttat aagggatttt 5880
gccgatttcg gcctattggt taaaaaatga gctgatttaa caaaaattta acgcgaattt 5940
taacaaaata ttaacgctta caatttaggt ggcacttttc ggggaaatgt gcgcggaacc 6000
cctatttgtt tatttttcta aatacattca aatatgtatc cgctcatgag acaataaccc 6060
tgataaatgc ttcaataata ttgaaaaagg aagagtatga gtattcaaca tttccgtgtc 6120
gcccttattc ccttttttgc ggcattttgc cttcctgttt ttgctcaccc agaaacgctg 6180
gtgaaagtaa aagatgctga agatcagttg ggtgcacgag tgggttacat cgaactggat 6240
ctcaacagcg gtaagatcct tgagagtttt cgccccgaag aacgttttcc aatgatgagc 6300
acttttaaag ttctgctatg tggcgcggta ttatcccgta ttgacgccgg gcaagagcaa 6360
ctcggtcgcc gcatacacta ttctcagaat gacttggttg agtactcacc agtcacagaa 6420
aagcatctta cggatggcat gacagtaaga gaattatgca gtgctgccat aaccatgagt 6480
gataacactg cggccaactt acttctgaca acgatcggag gaccgaagga gctaaccgct 6540
tttttgcaca acatggggga tcatgtaact cgccttgatc gttgggaacc ggagctgaat 6600
gaagccatac caaacgacga gcgtgacacc acgatgcctg tagcaatggc aacaacgttg 6660
cgcaaactat taactggcga actacttact ctagcttccc ggcaacaatt aatagactgg 6720
atggaggcgg ataaagttgc aggaccactt ctgcgctcgg cccttccggc tggctggttt 6780
attgctgata aatctggagc cggtgagcgt ggttctcgcg gtatcattgc agcactgggg 6840
ccagatggta agccctcccg tatcgtagtt atctacacga cggggagtca ggcaactatg 6900
gatgaacgaa atagacagat cgctgagata ggtgcctcac tgattaagca ttggtaactg 6960
tcagaccaag tttactcata tatactttag attgatttaa aacttcattt ttaatttaaa 7020
aggatctagg tgaagatcct ttttgataat ctcatgacca aaatccctta acgtgagttt 7080
tcgttccact gagcgtcaga ccccgtagaa aagatcaaag gatcttcttg agatcctttt 7140
tttctgcgcg taatctgctg cttgcaaaca aaaaaaccac cgctaccagc ggtggtttgt 7200
ttgccggatc aagagctacc aactcttttt ccgaaggtaa ctggcttcag cagagcgcag 7260
ataccaaata ctgttcttct agtgtagccg tagttaggcc accacttcaa gaactctgta 7320
gcaccgccta catacctcgc tctgctaatc ctgttaccag tggctgctgc cagtggcgat 7380
aagtcgtgtc ttaccgggtt ggactcaaga cgatagttac cggataaggc gcagcggtcg 7440
ggctgaacgg ggggttcgtg cacacagccc agcttggagc gaacgaccta caccgaactg 7500
agatacctac agcgtgagct atgagaaagc gccacgcttc ccgaagggag aaaggcggac 7560
aggtatccgg taagcggcag ggtcggaaca ggagagcgca cgagggagct tccaggggga 7620
aacgcctggt atctttatag tcctgtcggg tttcgccacc tctgacttga gcgtcgattt 7680
ttgtgatgct cgtcaggggg gcggagccta tggaaaaacg ccagcaacgc ggccttttta 7740
cggttcctgg ccttttgctg gccttttgct cacatggtct ttcctgcgtt atcccctgat 7800
tctgtggata accgtattac cgcctttgag tgagctgata ccgctcgccg cagccgaacg 7860
accgagcgca gcgagtcagt gagcgaggaa gcggagagcg cccaatacgc aaaccgcctc 7920
tccccgcgcg ttggccgatt cattaatgca gctggcacga caggtttccc gactggaaag 7980
cgggcagtga gcgcaacgca attaatgtga gttagctcac tcattaggca ccccaggctt 8040
tacactttat gcttccggct cgtatgttgt gtggaattgt gagcggataa caatttcaca 8100
caggaaacag ctatgaccat gattacgcca agcgcgtcaa ttaaccctca ctaaagggaa 8160
caaaagctgt taattaa 8177
<210> 67
<211> 6349
<212> DNA
<213> artificial sequence
<220>
<223> Matrice PD1 locus_IL12a_2A_IL12b pCLS30511 full sequence
<400> 67
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240
attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300
tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360
tttcccagtc acgacgttgt aaaacgacgg ccagtgaatt cgagctcggt acctcgcgaa 420
tgcatctaga tgactcccca gacaggccct ggaacccccc caccttctcc ccagccctgc 480
tcgtggtgac cgaaggggac aacgccacct tcacctgcag cttctccaac acatcggaga 540
gcttcgtgct aaactggtac cgcatgagcc ccagcaacca gacggacaag ctggccgcct 600
tccccgagga ccgcagccag cccggccagg actgccgctt ccgtgtcaca caactgccca 660
acgggcgtga cttccacatg agcgtggtca gggcccggcg caatgacagc ggcacctacc 720
tctgtggggc cggttctggc gtgaaacaga ctttgaattt tgaccttctc aagttggcgg 780
gagacgtgga gtccaaccca gggcccatgt ggccccctgg gtcagcctcc cagccaccgc 840
cctcacctgc cgcggccaca ggtctgcatc cagcggctcg ccctgtgtcc ctgcagtgcc 900
ggctcagcat gtgtccagcg cgcagcctcc tccttgtggc taccctggtc ctcctggacc 960
acctcagttt ggccagaaac ctccccgtgg ccactccaga cccaggaatg ttcccatgcc 1020
ttcaccactc ccaaaacctg ctgagggccg tcagcaacat gctccagaag gccagacaaa 1080
ctctagaatt ttacccttgc acttctgaag agattgatca tgaagatatc acaaaagata 1140
aaaccagcac agtggaggcc tgtttaccat tggaattaac caagaatgag agttgcctaa 1200
attccagaga gacctctttc ataactaatg ggagttgcct ggcctccaga aagacctctt 1260
ttatgatggc cctgtgcctt agtagtattt atgaagactt gaagatgtac caggtggagt 1320
tcaagaccat gaatgcaaag cttctgatgg atcctaagag gcagatcttt ctagatcaaa 1380
acatgctggc agttattgat gagctgatgc aggccctgaa tttcaacagt gagactgtgc 1440
cacaaaaatc ctcccttgaa gaaccggatt tttataaaac taaaatcaag ctctgcatac 1500
ttcttcatgc tttcagaatt cgggcagtga ctattgatag agtgatgagc tatctgaatg 1560
cttccggaag cggagctact aacttcagcc tgctgaagca ggctggagac gtggaggaga 1620
accctggacc tatgtgtcac cagcagttgg tcatctcttg gttttccctg gtttttctgg 1680
catctcccct cgtggccata tgggaactga agaaagatgt ttatgtcgta gaattggatt 1740
ggtatccgga tgcccctgga gaaatggtgg tcctcacctg tgacacccct gaagaagatg 1800
gtatcacctg gaccttggac cagagcagtg aggtcttagg ctctggcaaa accctgacca 1860
tccaagtcaa agagtttgga gatgctggcc agtacacctg tcacaaagga ggcgaggttc 1920
taagccattc gctcctgctg cttcacaaaa aggaagatgg aatttggtcc actgatattt 1980
taaaggacca gaaagaaccc aaaaataaga cctttctaag atgcgaggcc aagaattatt 2040
ctggacgttt cacctgctgg tggctgacga caatcagtac tgatttgaca ttcagtgtca 2100
aaagcagcag aggctcttct gacccccaag gggtgacgtg cggagctgct acactctctg 2160
cagagagagt cagaggggac aacaaggagt atgagtactc agtggagtgc caggaggaca 2220
gtgcctgccc agctgctgag gagagtctgc ccattgaggt catggtggat gccgttcaca 2280
agctcaagta tgaaaactac accagcagct tcttcatcag ggacatcatc aaacctgacc 2340
cacccaagaa cttgcagctg aagccattaa agaattctcg gcaggtggag gtcagctggg 2400
agtaccctga cacctggagt actccacatt cctacttctc cctgacattc tgcgttcagg 2460
tccagggcaa gagcaagaga gaaaagaaag atagagtctt cacggacaag acctcagcca 2520
cggtcatctg ccgcaaaaat gccagcatta gcgtgcgggc ccaggaccgc tactatagct 2580
catcttggag cgaatgggca tctgtgccct gcagtgaggg cagaggcagc ctgctgacct 2640
gcggcgacgt cgaggagaac cccgggccca tgggggcagg tgccaccggc cgcgccatgg 2700
acgggccgcg cctgctgctg ttgctgcttc tgggggtgtc ccttggaggt gccaaggagg 2760
catgccccac aggcctgtac acacacagcg gtgagtgctg caaagcctgc aacctgggcg 2820
agggtgtggc ccagccttgt ggagccaacc agaccgtgtg tgagccctgc ctggacagcg 2880
tgacgttctc cgacgtggtg agcgcgaccg agccgtgcaa gccgtgcacc gagtgcgtgg 2940
ggctccagag catgtcggcg ccgtgcgtgg aggccgatga cgccgtgtgc cgctgcgcct 3000
acggctacta ccaggatgag acgactgggc gctgcgaggc gtgccgcgtg tgcgaggcgg 3060
gctcgggcct cgtgttctcc tgccaggaca agcagaacac cgtgtgcgag gagtgccccg 3120
acggcacgta ttccgacgag gccaaccacg tggacccgtg cctgccctgc accgtgtgcg 3180
aggacaccga gcgccagctc cgcgagtgca cacgctgggc cgacgccgag tgcgaggaga 3240
tccctggccg ttggattaca cggtccacac ccccagaggg ctcggacagc acagccccca 3300
gcacccagga gcctgaggca cctccagaac aagacctcat agccagcacg gtggcaggtg 3360
tggtgaccac agtgatgggc agctcccagc ccgtggtgac ccgaggcacc accgacaacc 3420
tcatccctgt ctattgctcc atcctggctg ctgtggttgt gggtcttgtg gcctacatag 3480
ccttcaagag gtgatctaga gggcccgttt aaacccgctg atcagcctcg actgtgcctt 3540
ctagttgcca gccatctgtt gtttgcccct cccccgtgcc ttccttgacc ctggaaggtg 3600
ccactcccac tgtcctttcc taataaaatg aggaaattgc atcgcattgt ctgagtaggt 3660
gtcattctat tctggggggt ggggtggggc aggacagcaa gggggaggat tgggaagaca 3720
atagcaggca tgctggggat gcggtgggct ctatgactag tggcgaattc ggcgcagatc 3780
aaagagagcc tgcgggcaga gctcagggtg acaggtgcgg cctcggaggc cccggggcag 3840
gggtgagctg agccggtcct ggggtgggtg tcccctcctg cacaggatca ggagctccag 3900
ggtcgtaggg cagggacccc ccagctccag tccagggctc tgtcctgcac ctggggaatg 3960
gtgaccggca tctctgtcct ctagctctgg aagcacccca gcccctctag tctgccctca 4020
cccctgaccc tgaccctcca ccctgacccc gtcctaaccc ctgacctttg atcggatccc 4080
gggcccgtcg actgcagagg cctgcatgca agcttggcgt aatcatggtc atagctgttt 4140
cctgtgtgaa attgttatcc gctcacaatt ccacacaaca tacgagccgg aagcataaag 4200
tgtaaagcct ggggtgccta atgagtgagc taactcacat taattgcgtt gcgctcactg 4260
cccgctttcc agtcgggaaa cctgtcgtgc cagctgcatt aatgaatcgg ccaacgcgcg 4320
gggagaggcg gtttgcgtat tgggcgctct tccgcttcct cgctcactga ctcgctgcgc 4380
tcggtcgttc ggctgcggcg agcggtatca gctcactcaa aggcggtaat acggttatcc 4440
acagaatcag gggataacgc aggaaagaac atgtgagcaa aaggccagca aaaggccagg 4500
aaccgtaaaa aggccgcgtt gctggcgttt ttccataggc tccgcccccc tgacgagcat 4560
cacaaaaatc gacgctcaag tcagaggtgg cgaaacccga caggactata aagataccag 4620
gcgtttcccc ctggaagctc cctcgtgcgc tctcctgttc cgaccctgcc gcttaccgga 4680
tacctgtccg cctttctccc ttcgggaagc gtggcgcttt ctcatagctc acgctgtagg 4740
tatctcagtt cggtgtaggt cgttcgctcc aagctgggct gtgtgcacga accccccgtt 4800
cagcccgacc gctgcgcctt atccggtaac tatcgtcttg agtccaaccc ggtaagacac 4860
gacttatcgc cactggcagc agccactggt aacaggatta gcagagcgag gtatgtaggc 4920
ggtgctacag agttcttgaa gtggtggcct aactacggct acactagaag aacagtattt 4980
ggtatctgcg ctctgctgaa gccagttacc ttcggaaaaa gagttggtag ctcttgatcc 5040
ggcaaacaaa ccaccgctgg tagcggtggt ttttttgttt gcaagcagca gattacgcgc 5100
agaaaaaaag gatctcaaga agatcctttg atcttttcta cggggtctga cgctcagtgg 5160
aacgaaaact cacgttaagg gattttggtc atgagattat caaaaaggat cttcacctag 5220
atccttttaa attaaaaatg aagttttaaa tcaatctaaa gtatatatga gtaaacttgg 5280
tctgacagtt accaatgctt aatcagtgag gcacctatct cagcgatctg tctatttcgt 5340
tcatccatag ttgcctgact ccccgtcgtg tagataacta cgatacggga gggcttacca 5400
tctggcccca gtgctgcaat gataccgcga gacccacgct caccggctcc agatttatca 5460
gcaataaacc agccagccgg aagggccgag cgcagaagtg gtcctgcaac tttatccgcc 5520
tccatccagt ctattaattg ttgccgggaa gctagagtaa gtagttcgcc agttaatagt 5580
ttgcgcaacg ttgttgccat tgctacaggc atcgtggtgt cacgctcgtc gtttggtatg 5640
gcttcattca gctccggttc ccaacgatca aggcgagtta catgatcccc catgttgtgc 5700
aaaaaagcgg ttagctcctt cggtcctccg atcgttgtca gaagtaagtt ggccgcagtg 5760
ttatcactca tggttatggc agcactgcat aattctctta ctgtcatgcc atccgtaaga 5820
tgcttttctg tgactggtga gtactcaacc aagtcattct gagaatagtg tatgcggcga 5880
ccgagttgct cttgcccggc gtcaatacgg gataataccg cgccacatag cagaacttta 5940
aaagtgctca tcattggaaa acgttcttcg gggcgaaaac tctcaaggat cttaccgctg 6000
ttgagatcca gttcgatgta acccactcgt gcacccaact gatcttcagc atcttttact 6060
ttcaccagcg tttctgggtg agcaaaaaca ggaaggcaaa atgccgcaaa aaagggaata 6120
agggcgacac ggaaatgttg aatactcata ctcttccttt ttcaatatta ttgaagcatt 6180
tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa aaataaacaa 6240
ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtctaaga aaccattatt 6300
atcatgacat taacctataa aaataggcgt atcacgaggc cctttcgtc 6349
<210> 68
<211> 2489
<212> DNA
<213> artificial sequence
<220>
<223> HLAE trimer matrix (VMAPRTLFL peptide) inserted at the B2m locus
<400> 68
cacttagcat ctctggggcc agtctgcaaa gcgagggggc agccttaatg tgcctccagc 60
ctgaagtcct agaatgagcg cccggtgtcc caagctgggg cgcgcacccc agatcggagg 120
gcgccgatgt acagacagca aactcaccca gtctagtgca tgccttctta aacatcacga 180
gactctaaga aaaggaaact gaaaacggga aagtccctct ctctaacctg gcactgcgtc 240
gctggcttgg agacaggtga cggtccctgc gggccttgtc ctgattggct gggcacgcgt 300
ttaatataag tggaggcgtc gcgctggcgg gcattcctga agctgacagc attcgggccg 360
agatgtctcg ctccgtggcc ttagctgtgc tcgcgctact ctctcttagc ggcctcgaag 420
ctgttatggc tccgcggact ttattcttag gtggtggcgg atccggtggt ggcggttctg 480
gtggtggcgg ctccatccag cgtacgccca aaattcaagt ctacagccga catcctgcag 540
agaacggcaa atctaatttc ctgaactgct atgtatcagg ctttcaccct agcgatatag 600
aagtggacct gctgaaaaac ggagagagga tagaaaaggt cgaacacagc gacctctcct 660
tttccaagga ctggagcttt tatcttctgt attatactga atttacaccc acggaaaaag 720
atgagtatgc gtgccgagta aaccacgtca cgctgtcaca gcccaaaata gtaaaatggg 780
atcgcgacat gggtggtggc ggttctggtg gtggcggtag tggcggcgga ggaagcggtg 840
gtggcggttc cggatctcac tccttgaagt atttccacac ttccgtgtcc cggcccggcc 900
gcggggagcc ccgcttcatc tctgtgggct acgtggacga cacccagttc gtgcgcttcg 960
acaacgacgc cgcgagtccg aggatggtgc cgcgggcgcc gtggatggag caggaggggt 1020
cagagtattg ggaccgggag acacggagcg ccagggacac cgcacagatt ttccgagtga 1080
acctgcggac gctgcgcggc tactacaatc agagcgaggc cgggtctcac accctgcagt 1140
ggatgcatgg ctgcgagctg gggcccgaca ggcgcttcct ccgcgggtat gaacagttcg 1200
cctacgacgg caaggattat ctcaccctga atgaggacct gcgctcctgg accgcggtgg 1260
acacggcggc tcagatctcc gagcaaaagt caaatgatgc ctctgaggcg gagcaccaga 1320
gagcctacct ggaagacaca tgcgtggagt ggctccacaa atacctggag aaggggaagg 1380
agacgctgct tcacctggag cccccaaaga cacacgtgac tcaccacccc atctctgacc 1440
atgaggccac cctgaggtgc tgggctctgg gcttctaccc tgcggagatc acactgacct 1500
ggcagcagga tggggagggc catacccagg acacggagct cgtggagacc aggcctgcag 1560
gggatggaac cttccagaag tgggcagctg tggtggtgcc ttctggagag gagcagagat 1620
acacgtgcca tgtgcagcat gaggggctac ccgagcccgt caccctgaga tggaagccgg 1680
cttcccagcc caccatcccc atcgtgggca tcattgctgg cctggttctc cttggatctg 1740
tggtctctgg agctgtggtt gctgctgtga tatggaggaa gaagagctca ggtggaaaag 1800
gagggagcta ctataaggct gagtggagcg acagtgccca ggggtctgag tctcacagct 1860
tgtaactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt 1920
gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca 1980
ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga 2040
ggattgggaa gacaatagca ggcatgctgg ggatgcggtg ggctctatgt ctctttctgg 2100
cctggaggct atccagcgtg agtctctcct accctcccgc tctggtcctt cctctcccgc 2160
tctgcaccct ctgtggccct cgctgtgctc tctcgctccg tgacttccct tctccaagtt 2220
ctccttggtg gcccgccgtg gggctagtcc agggctggat ctcggggaag cggcggggtg 2280
gcctgggagt ggggaagggg gtgcgcaccc gggacgcgcg ctacttgccc ctttcggcgg 2340
ggagcagggg agacctttgg cctacggcga cgggagggtc gggacaaagt ttagggcgtc 2400
gataagcgtc agagcgccga ggttggggga gggtttctct tccgctcttt cgcggggcct 2460
ctggctcccc cagcgcagct ggagtgggg 2489
<210> 69
<211> 2289
<212> DNA
<213> artificial sequence
<220>
<223> HLAE trimer matrix (VMAPRTLFL peptide)
<400> 69
cgcgcacccc agatcggagg gcgccgatgt acagacagca aactcaccca gtctagtgca 60
tgccttctta aacatcacga gactctaaga aaaggaaact gaaaacggga aagtccctct 120
ctctaacctg gcactgcgtc gctggcttgg agacaggtga cggtccctgc gggccttgtc 180
ctgattggct gggcacgcgt ttaatataag tggaggcgtc gcgctggcgg gcattcctga 240
agctgacagc attcgggccg agatgtctcg ctccgtggcc ttagctgtgc tcgcgctact 300
ctctcttagc ggcctcgaag ctgttatggc tccgcggact ttattcttag gtggtggcgg 360
atccggtggt ggcggttctg gtggtggcgg ctccatccag cgtacgccca aaattcaagt 420
ctacagccga catcctgcag agaacggcaa atctaatttc ctgaactgct atgtatcagg 480
ctttcaccct agcgatatag aagtggacct gctgaaaaac ggagagagga tagaaaaggt 540
cgaacacagc gacctctcct tttccaagga ctggagcttt tatcttctgt attatactga 600
atttacaccc acggaaaaag atgagtatgc gtgccgagta aaccacgtca cgctgtcaca 660
gcccaaaata gtaaaatggg atcgcgacat gggtggtggc ggttctggtg gtggcggtag 720
tggcggcgga ggaagcggtg gtggcggttc cggatctcac tccttgaagt atttccacac 780
ttccgtgtcc cggcccggcc gcggggagcc ccgcttcatc tctgtgggct acgtggacga 840
cacccagttc gtgcgcttcg acaacgacgc cgcgagtccg aggatggtgc cgcgggcgcc 900
gtggatggag caggaggggt cagagtattg ggaccgggag acacggagcg ccagggacac 960
cgcacagatt ttccgagtga acctgcggac gctgcgcggc tactacaatc agagcgaggc 1020
cgggtctcac accctgcagt ggatgcatgg ctgcgagctg gggcccgaca ggcgcttcct 1080
ccgcgggtat gaacagttcg cctacgacgg caaggattat ctcaccctga atgaggacct 1140
gcgctcctgg accgcggtgg acacggcggc tcagatctcc gagcaaaagt caaatgatgc 1200
ctctgaggcg gagcaccaga gagcctacct ggaagacaca tgcgtggagt ggctccacaa 1260
atacctggag aaggggaagg agacgctgct tcacctggag cccccaaaga cacacgtgac 1320
tcaccacccc atctctgacc atgaggccac cctgaggtgc tgggctctgg gcttctaccc 1380
tgcggagatc acactgacct ggcagcagga tggggagggc catacccagg acacggagct 1440
cgtggagacc aggcctgcag gggatggaac cttccagaag tgggcagctg tggtggtgcc 1500
ttctggagag gagcagagat acacgtgcca tgtgcagcat gaggggctac ccgagcccgt 1560
caccctgaga tggaagccgg cttcccagcc caccatcccc atcgtgggca tcattgctgg 1620
cctggttctc cttggatctg tggtctctgg agctgtggtt gctgctgtga tatggaggaa 1680
gaagagctca ggtggaaaag gagggagcta ctataaggct gagtggagcg acagtgccca 1740
ggggtctgag tctcacagct tgtaactgtg ccttctagtt gccagccatc tgttgtttgc 1800
ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa 1860
aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg 1920
gggcaggaca gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg 1980
ggctctatgt ctctttctgg cctggaggct atccagcgtg agtctctcct accctcccgc 2040
tctggtcctt cctctcccgc tctgcaccct ctgtggccct cgctgtgctc tctcgctccg 2100
tgacttccct tctccaagtt ctccttggtg gcccgccgtg gggctagtcc agggctggat 2160
ctcggggaag cggcggggtg gcctgggagt ggggaagggg gtgcgcaccc gggacgcgcg 2220
ctacttgccc ctttcggcgg ggagcagggg agacctttgg cctacggcga cgggagggtc 2280
gggacaaag 2289
<210> 70
<211> 2489
<212> DNA
<213> artificial sequence
<220>
<223> HLAE trimer matrix (VMAPRTLIL peptide) inserted at the B2m locus
<400> 70
cacttagcat ctctggggcc agtctgcaaa gcgagggggc agccttaatg tgcctccagc 60
ctgaagtcct agaatgagcg cccggtgtcc caagctgggg cgcgcacccc agatcggagg 120
gcgccgatgt acagacagca aactcaccca gtctagtgca tgccttctta aacatcacga 180
gactctaaga aaaggaaact gaaaacggga aagtccctct ctctaacctg gcactgcgtc 240
gctggcttgg agacaggtga cggtccctgc gggccttgtc ctgattggct gggcacgcgt 300
ttaatataag tggaggcgtc gcgctggcgg gcattcctga agctgacagc attcgggccg 360
agatgtctcg ctccgtggcc ttagctgtgc tcgcgctact ctctcttagc ggcctcgaag 420
ctgttatggc tccgcggact ttaattttag gtggtggcgg atccggtggt ggcggttctg 480
gtggtggcgg ctccatccag cgtacgccca aaattcaagt ctacagccga catcctgcag 540
agaacggcaa atctaatttc ctgaactgct atgtatcagg ctttcaccct agcgatatag 600
aagtggacct gctgaaaaac ggagagagga tagaaaaggt cgaacacagc gacctctcct 660
tttccaagga ctggagcttt tatcttctgt attatactga atttacaccc acggaaaaag 720
atgagtatgc gtgccgagta aaccacgtca cgctgtcaca gcccaaaata gtaaaatggg 780
atcgcgacat gggtggtggc ggttctggtg gtggcggtag tggcggcgga ggaagcggtg 840
gtggcggttc cggatctcac tccttgaagt atttccacac ttccgtgtcc cggcccggcc 900
gcggggagcc ccgcttcatc tctgtgggct acgtggacga cacccagttc gtgcgcttcg 960
acaacgacgc cgcgagtccg aggatggtgc cgcgggcgcc gtggatggag caggaggggt 1020
cagagtattg ggaccgggag acacggagcg ccagggacac cgcacagatt ttccgagtga 1080
acctgcggac gctgcgcggc tactacaatc agagcgaggc cgggtctcac accctgcagt 1140
ggatgcatgg ctgcgagctg gggcccgaca ggcgcttcct ccgcgggtat gaacagttcg 1200
cctacgacgg caaggattat ctcaccctga atgaggacct gcgctcctgg accgcggtgg 1260
acacggcggc tcagatctcc gagcaaaagt caaatgatgc ctctgaggcg gagcaccaga 1320
gagcctacct ggaagacaca tgcgtggagt ggctccacaa atacctggag aaggggaagg 1380
agacgctgct tcacctggag cccccaaaga cacacgtgac tcaccacccc atctctgacc 1440
atgaggccac cctgaggtgc tgggctctgg gcttctaccc tgcggagatc acactgacct 1500
ggcagcagga tggggagggc catacccagg acacggagct cgtggagacc aggcctgcag 1560
gggatggaac cttccagaag tgggcagctg tggtggtgcc ttctggagag gagcagagat 1620
acacgtgcca tgtgcagcat gaggggctac ccgagcccgt caccctgaga tggaagccgg 1680
cttcccagcc caccatcccc atcgtgggca tcattgctgg cctggttctc cttggatctg 1740
tggtctctgg agctgtggtt gctgctgtga tatggaggaa gaagagctca ggtggaaaag 1800
gagggagcta ctataaggct gagtggagcg acagtgccca ggggtctgag tctcacagct 1860
tgtaactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt 1920
gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca 1980
ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga 2040
ggattgggaa gacaatagca ggcatgctgg ggatgcggtg ggctctatgt ctctttctgg 2100
cctggaggct atccagcgtg agtctctcct accctcccgc tctggtcctt cctctcccgc 2160
tctgcaccct ctgtggccct cgctgtgctc tctcgctccg tgacttccct tctccaagtt 2220
ctccttggtg gcccgccgtg gggctagtcc agggctggat ctcggggaag cggcggggtg 2280
gcctgggagt ggggaagggg gtgcgcaccc gggacgcgcg ctacttgccc ctttcggcgg 2340
ggagcagggg agacctttgg cctacggcga cgggagggtc gggacaaagt ttagggcgtc 2400
gataagcgtc agagcgccga ggttggggga gggtttctct tccgctcttt cgcggggcct 2460
ctggctcccc cagcgcagct ggagtgggg 2489
<210> 71
<211> 2289
<212> DNA
<213> artificial sequence
<220>
<223> HLAE trimer matrix (VMAPRTLIL peptide)
<400> 71
cgcgcacccc agatcggagg gcgccgatgt acagacagca aactcaccca gtctagtgca 60
tgccttctta aacatcacga gactctaaga aaaggaaact gaaaacggga aagtccctct 120
ctctaacctg gcactgcgtc gctggcttgg agacaggtga cggtccctgc gggccttgtc 180
ctgattggct gggcacgcgt ttaatataag tggaggcgtc gcgctggcgg gcattcctga 240
agctgacagc attcgggccg agatgtctcg ctccgtggcc ttagctgtgc tcgcgctact 300
ctctcttagc ggcctcgaag ctgttatggc tccgcggact ttaattttag gtggtggcgg 360
atccggtggt ggcggttctg gtggtggcgg ctccatccag cgtacgccca aaattcaagt 420
ctacagccga catcctgcag agaacggcaa atctaatttc ctgaactgct atgtatcagg 480
ctttcaccct agcgatatag aagtggacct gctgaaaaac ggagagagga tagaaaaggt 540
cgaacacagc gacctctcct tttccaagga ctggagcttt tatcttctgt attatactga 600
atttacaccc acggaaaaag atgagtatgc gtgccgagta aaccacgtca cgctgtcaca 660
gcccaaaata gtaaaatggg atcgcgacat gggtggtggc ggttctggtg gtggcggtag 720
tggcggcgga ggaagcggtg gtggcggttc cggatctcac tccttgaagt atttccacac 780
ttccgtgtcc cggcccggcc gcggggagcc ccgcttcatc tctgtgggct acgtggacga 840
cacccagttc gtgcgcttcg acaacgacgc cgcgagtccg aggatggtgc cgcgggcgcc 900
gtggatggag caggaggggt cagagtattg ggaccgggag acacggagcg ccagggacac 960
cgcacagatt ttccgagtga acctgcggac gctgcgcggc tactacaatc agagcgaggc 1020
cgggtctcac accctgcagt ggatgcatgg ctgcgagctg gggcccgaca ggcgcttcct 1080
ccgcgggtat gaacagttcg cctacgacgg caaggattat ctcaccctga atgaggacct 1140
gcgctcctgg accgcggtgg acacggcggc tcagatctcc gagcaaaagt caaatgatgc 1200
ctctgaggcg gagcaccaga gagcctacct ggaagacaca tgcgtggagt ggctccacaa 1260
atacctggag aaggggaagg agacgctgct tcacctggag cccccaaaga cacacgtgac 1320
tcaccacccc atctctgacc atgaggccac cctgaggtgc tgggctctgg gcttctaccc 1380
tgcggagatc acactgacct ggcagcagga tggggagggc catacccagg acacggagct 1440
cgtggagacc aggcctgcag gggatggaac cttccagaag tgggcagctg tggtggtgcc 1500
ttctggagag gagcagagat acacgtgcca tgtgcagcat gaggggctac ccgagcccgt 1560
caccctgaga tggaagccgg cttcccagcc caccatcccc atcgtgggca tcattgctgg 1620
cctggttctc cttggatctg tggtctctgg agctgtggtt gctgctgtga tatggaggaa 1680
gaagagctca ggtggaaaag gagggagcta ctataaggct gagtggagcg acagtgccca 1740
ggggtctgag tctcacagct tgtaactgtg ccttctagtt gccagccatc tgttgtttgc 1800
ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa 1860
aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg 1920
gggcaggaca gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg 1980
ggctctatgt ctctttctgg cctggaggct atccagcgtg agtctctcct accctcccgc 2040
tctggtcctt cctctcccgc tctgcaccct ctgtggccct cgctgtgctc tctcgctccg 2100
tgacttccct tctccaagtt ctccttggtg gcccgccgtg gggctagtcc agggctggat 2160
ctcggggaag cggcggggtg gcctgggagt ggggaagggg gtgcgcaccc gggacgcgcg 2220
ctacttgccc ctttcggcgg ggagcagggg agacctttgg cctacggcga cgggagggtc 2280
gggacaaag 2289
<210> 72
<211> 2531
<212> DNA
<213> artificial sequence
<220>
<223> UL18Trimer matrix _Actine peptide inserted at the B2m locus
<400> 72
cacttagcat ctctggggcc agtctgcaaa gcgagggggc agccttaatg tgcctccagc 60
ctgaagtcct agaatgagcg cccggtgtcc caagctgggg cgcgcacccc agatcggagg 120
gcgccgatgt acagacagca aactcaccca gtctagtgca tgccttctta aacatcacga 180
gactctaaga aaaggaaact gaaaacggga aagtccctct ctctaacctg gcactgcgtc 240
gctggcttgg agacaggtga cggtccctgc gggccttgtc ctgattggct gggcacgcgt 300
ttaatataag tggaggcgtc gcgctggcgg gcattcctga agctgacagc attcgggccg 360
agatgtctcg ctccgtggcc ttagctgtgc tcgcgctact ctctcttagc ggcctcgaag 420
ctgccctgcc ccacgccatt ttgcggctcg gtggtggcgg atccggtggt ggcggttctg 480
gtggtggcgg ctccatccag cgtacgccca aaattcaagt ctacagccga catcctgcag 540
agaacggcaa atctaatttc ctgaactgct atgtatcagg ctttcaccct agcgatatag 600
aagtggacct gctgaaaaac ggagagagga tagaaaaggt cgaacacagc gacctctcct 660
tttccaagga ctggagcttt tatcttctgt attatactga atttacaccc acggaaaaag 720
atgagtatgc gtgccgagta aaccacgtca cgctgtcaca gcccaaaata gtaaaatggg 780
atcgcgacat gggtggtggc ggttctggtg gtggcggtag tggcggcgga ggaagcggtg 840
gtggcggttc cggatctatg cacgtgctga gatacggata taccggcatc ttcgacgata 900
catcccatat gactctgacc gtggtcggga tttttgacgg acagcacttc tttacatacc 960
atgtgaacag ctccgataag gcttctagtc gagcaaatgg caccatctca tggatggcca 1020
acgtgagcgc agcctacccc acatatctgg acggagaacg cgctaaaggc gatctgatct 1080
tcaatcagac cgagcagaac ctgctggagc tggaaattgc tctggggtac aggtctcaga 1140
gtgtcctgac atggactcac gaatgtaata ccacagagaa cgggagcttc gtggcaggat 1200
atgagggctt tgggtgggac ggagaaacac tgatggagct gaaggataat ctgactctgt 1260
ggaccggccc taactacgaa atcagctggc tgaagcagaa caagacttac atcgacggaa 1320
agatcaaaaa catcagcgag ggcgatacta ccatccagcg caattacctg aagggcaact 1380
gcacccagtg gagcgtgatc tactctgggt tccagacacc tgtcactcac ccagtggtca 1440
aagggggagt gcgaaaccag aatgacaacc gggccgaggc cttctgtaca tcctacggct 1500
tctttcccgg ggagatcaat attactttta tccattacgg caacaaggcc cccgacgatt 1560
ctgagcctca gtgcaatccc ctgctgccta ccttcgatgg cacatttcac caggggtgct 1620
acgtcgctat cttctgcaat cagaactata cttgccgggt gacccatggg aactggactg 1680
tggaaatccc aatttcagtc accagccccg acgattcaag ctccggagag gtgccagatc 1740
accccaccgc aaataagaga tacaacacca tgacaatctc tagtgtgctg ctggccctgc 1800
tgctgtgcgc actgctgttc gcttttctgc attacttcac aactctgaag cagtatctgc 1860
ggaacctggc atttgcctgg cggtacagaa aagtgagatc aagctgactg tgccttctag 1920
ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 1980
tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 2040
ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag 2100
caggcatgct ggggatgcgg tgggctctat gtctctttct ggcctggagg ctatccagcg 2160
tgagtctctc ctaccctccc gctctggtcc ttcctctccc gctctgcacc ctctgtggcc 2220
ctcgctgtgc tctctcgctc cgtgacttcc cttctccaag ttctccttgg tggcccgccg 2280
tggggctagt ccagggctgg atctcgggga agcggcgggg tggcctggga gtggggaagg 2340
gggtgcgcac ccgggacgcg cgctacttgc ccctttcggc ggggagcagg ggagaccttt 2400
ggcctacggc gacgggaggg tcgggacaaa gtttagggcg tcgataagcg tcagagcgcc 2460
gaggttgggg gagggtttct cttccgctct ttcgcggggc ctctggctcc cccagcgcag 2520
ctggagtggg g 2531
<210> 73
<211> 2331
<212> DNA
<213> artificial sequence
<220>
<223> UL18Trimer matrix _Actine peptide
<400> 73
cgcgcacccc agatcggagg gcgccgatgt acagacagca aactcaccca gtctagtgca 60
tgccttctta aacatcacga gactctaaga aaaggaaact gaaaacggga aagtccctct 120
ctctaacctg gcactgcgtc gctggcttgg agacaggtga cggtccctgc gggccttgtc 180
ctgattggct gggcacgcgt ttaatataag tggaggcgtc gcgctggcgg gcattcctga 240
agctgacagc attcgggccg agatgtctcg ctccgtggcc ttagctgtgc tcgcgctact 300
ctctcttagc ggcctcgaag ctgccctgcc ccacgccatt ttgcggctcg gtggtggcgg 360
atccggtggt ggcggttctg gtggtggcgg ctccatccag cgtacgccca aaattcaagt 420
ctacagccga catcctgcag agaacggcaa atctaatttc ctgaactgct atgtatcagg 480
ctttcaccct agcgatatag aagtggacct gctgaaaaac ggagagagga tagaaaaggt 540
cgaacacagc gacctctcct tttccaagga ctggagcttt tatcttctgt attatactga 600
atttacaccc acggaaaaag atgagtatgc gtgccgagta aaccacgtca cgctgtcaca 660
gcccaaaata gtaaaatggg atcgcgacat gggtggtggc ggttctggtg gtggcggtag 720
tggcggcgga ggaagcggtg gtggcggttc cggatctatg cacgtgctga gatacggata 780
taccggcatc ttcgacgata catcccatat gactctgacc gtggtcggga tttttgacgg 840
acagcacttc tttacatacc atgtgaacag ctccgataag gcttctagtc gagcaaatgg 900
caccatctca tggatggcca acgtgagcgc agcctacccc acatatctgg acggagaacg 960
cgctaaaggc gatctgatct tcaatcagac cgagcagaac ctgctggagc tggaaattgc 1020
tctggggtac aggtctcaga gtgtcctgac atggactcac gaatgtaata ccacagagaa 1080
cgggagcttc gtggcaggat atgagggctt tgggtgggac ggagaaacac tgatggagct 1140
gaaggataat ctgactctgt ggaccggccc taactacgaa atcagctggc tgaagcagaa 1200
caagacttac atcgacggaa agatcaaaaa catcagcgag ggcgatacta ccatccagcg 1260
caattacctg aagggcaact gcacccagtg gagcgtgatc tactctgggt tccagacacc 1320
tgtcactcac ccagtggtca aagggggagt gcgaaaccag aatgacaacc gggccgaggc 1380
cttctgtaca tcctacggct tctttcccgg ggagatcaat attactttta tccattacgg 1440
caacaaggcc cccgacgatt ctgagcctca gtgcaatccc ctgctgccta ccttcgatgg 1500
cacatttcac caggggtgct acgtcgctat cttctgcaat cagaactata cttgccgggt 1560
gacccatggg aactggactg tggaaatccc aatttcagtc accagccccg acgattcaag 1620
ctccggagag gtgccagatc accccaccgc aaataagaga tacaacacca tgacaatctc 1680
tagtgtgctg ctggccctgc tgctgtgcgc actgctgttc gcttttctgc attacttcac 1740
aactctgaag cagtatctgc ggaacctggc atttgcctgg cggtacagaa aagtgagatc 1800
aagctgactg tgccttctag ttgccagcca tctgttgttt gcccctcccc cgtgccttcc 1860
ttgaccctgg aaggtgccac tcccactgtc ctttcctaat aaaatgagga aattgcatcg 1920
cattgtctga gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg 1980
gaggattggg aagacaatag caggcatgct ggggatgcgg tgggctctat gtctctttct 2040
ggcctggagg ctatccagcg tgagtctctc ctaccctccc gctctggtcc ttcctctccc 2100
gctctgcacc ctctgtggcc ctcgctgtgc tctctcgctc cgtgacttcc cttctccaag 2160
ttctccttgg tggcccgccg tggggctagt ccagggctgg atctcgggga agcggcgggg 2220
tggcctggga gtggggaagg gggtgcgcac ccgggacgcg cgctacttgc ccctttcggc 2280
ggggagcagg ggagaccttt ggcctacggc gacgggaggg tcgggacaaa g 2331
<210> 74
<211> 2531
<212> DNA
<213> artificial sequence
<220>
<223> UL18Trimer matrix _HLACw peptide inserted at the B2m locus
<400> 74
cacttagcat ctctggggcc agtctgcaaa gcgagggggc agccttaatg tgcctccagc 60
ctgaagtcct agaatgagcg cccggtgtcc caagctgggg cgcgcacccc agatcggagg 120
gcgccgatgt acagacagca aactcaccca gtctagtgca tgccttctta aacatcacga 180
gactctaaga aaaggaaact gaaaacggga aagtccctct ctctaacctg gcactgcgtc 240
gctggcttgg agacaggtga cggtccctgc gggccttgtc ctgattggct gggcacgcgt 300
ttaatataag tggaggcgtc gcgctggcgg gcattcctga agctgacagc attcgggccg 360
agatgtctcg ctccgtggcc ttagctgtgc tcgcgctact ctctcttagc ggcctcgaag 420
ctgttatggc tccgcggact ttaattttag gtggtggcgg atccggtggt ggcggttctg 480
gtggtggcgg ctccatccag cgtacgccca aaattcaagt ctacagccga catcctgcag 540
agaacggcaa atctaatttc ctgaactgct atgtatcagg ctttcaccct agcgatatag 600
aagtggacct gctgaaaaac ggagagagga tagaaaaggt cgaacacagc gacctctcct 660
tttccaagga ctggagcttt tatcttctgt attatactga atttacaccc acggaaaaag 720
atgagtatgc gtgccgagta aaccacgtca cgctgtcaca gcccaaaata gtaaaatggg 780
atcgcgacat gggtggtggc ggttctggtg gtggcggtag tggcggcgga ggaagcggtg 840
gtggcggttc cggatctatg cacgtgctga gatacggata taccggcatc ttcgacgata 900
catcccatat gactctgacc gtggtcggga tttttgacgg acagcacttc tttacatacc 960
atgtgaacag ctccgataag gcttctagtc gagcaaatgg caccatctca tggatggcca 1020
acgtgagcgc agcctacccc acatatctgg acggagaacg cgctaaaggc gatctgatct 1080
tcaatcagac cgagcagaac ctgctggagc tggaaattgc tctggggtac aggtctcaga 1140
gtgtcctgac atggactcac gaatgtaata ccacagagaa cgggagcttc gtggcaggat 1200
atgagggctt tgggtgggac ggagaaacac tgatggagct gaaggataat ctgactctgt 1260
ggaccggccc taactacgaa atcagctggc tgaagcagaa caagacttac atcgacggaa 1320
agatcaaaaa catcagcgag ggcgatacta ccatccagcg caattacctg aagggcaact 1380
gcacccagtg gagcgtgatc tactctgggt tccagacacc tgtcactcac ccagtggtca 1440
aagggggagt gcgaaaccag aatgacaacc gggccgaggc cttctgtaca tcctacggct 1500
tctttcccgg ggagatcaat attactttta tccattacgg caacaaggcc cccgacgatt 1560
ctgagcctca gtgcaatccc ctgctgccta ccttcgatgg cacatttcac caggggtgct 1620
acgtcgctat cttctgcaat cagaactata cttgccgggt gacccatggg aactggactg 1680
tggaaatccc aatttcagtc accagccccg acgattcaag ctccggagag gtgccagatc 1740
accccaccgc aaataagaga tacaacacca tgacaatctc tagtgtgctg ctggccctgc 1800
tgctgtgcgc actgctgttc gcttttctgc attacttcac aactctgaag cagtatctgc 1860
ggaacctggc atttgcctgg cggtacagaa aagtgagatc aagctgactg tgccttctag 1920
ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 1980
tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 2040
ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag 2100
caggcatgct ggggatgcgg tgggctctat gtctctttct ggcctggagg ctatccagcg 2160
tgagtctctc ctaccctccc gctctggtcc ttcctctccc gctctgcacc ctctgtggcc 2220
ctcgctgtgc tctctcgctc cgtgacttcc cttctccaag ttctccttgg tggcccgccg 2280
tggggctagt ccagggctgg atctcgggga agcggcgggg tggcctggga gtggggaagg 2340
gggtgcgcac ccgggacgcg cgctacttgc ccctttcggc ggggagcagg ggagaccttt 2400
ggcctacggc gacgggaggg tcgggacaaa gtttagggcg tcgataagcg tcagagcgcc 2460
gaggttgggg gagggtttct cttccgctct ttcgcggggc ctctggctcc cccagcgcag 2520
ctggagtggg g 2531
<210> 75
<211> 2331
<212> DNA
<213> artificial sequence
<220>
<223> UL18Trimer matrix _HLACw peptide
<400> 75
cgcgcacccc agatcggagg gcgccgatgt acagacagca aactcaccca gtctagtgca 60
tgccttctta aacatcacga gactctaaga aaaggaaact gaaaacggga aagtccctct 120
ctctaacctg gcactgcgtc gctggcttgg agacaggtga cggtccctgc gggccttgtc 180
ctgattggct gggcacgcgt ttaatataag tggaggcgtc gcgctggcgg gcattcctga 240
agctgacagc attcgggccg agatgtctcg ctccgtggcc ttagctgtgc tcgcgctact 300
ctctcttagc ggcctcgaag ctgttatggc tccgcggact ttaattttag gtggtggcgg 360
atccggtggt ggcggttctg gtggtggcgg ctccatccag cgtacgccca aaattcaagt 420
ctacagccga catcctgcag agaacggcaa atctaatttc ctgaactgct atgtatcagg 480
ctttcaccct agcgatatag aagtggacct gctgaaaaac ggagagagga tagaaaaggt 540
cgaacacagc gacctctcct tttccaagga ctggagcttt tatcttctgt attatactga 600
atttacaccc acggaaaaag atgagtatgc gtgccgagta aaccacgtca cgctgtcaca 660
gcccaaaata gtaaaatggg atcgcgacat gggtggtggc ggttctggtg gtggcggtag 720
tggcggcgga ggaagcggtg gtggcggttc cggatctatg cacgtgctga gatacggata 780
taccggcatc ttcgacgata catcccatat gactctgacc gtggtcggga tttttgacgg 840
acagcacttc tttacatacc atgtgaacag ctccgataag gcttctagtc gagcaaatgg 900
caccatctca tggatggcca acgtgagcgc agcctacccc acatatctgg acggagaacg 960
cgctaaaggc gatctgatct tcaatcagac cgagcagaac ctgctggagc tggaaattgc 1020
tctggggtac aggtctcaga gtgtcctgac atggactcac gaatgtaata ccacagagaa 1080
cgggagcttc gtggcaggat atgagggctt tgggtgggac ggagaaacac tgatggagct 1140
gaaggataat ctgactctgt ggaccggccc taactacgaa atcagctggc tgaagcagaa 1200
caagacttac atcgacggaa agatcaaaaa catcagcgag ggcgatacta ccatccagcg 1260
caattacctg aagggcaact gcacccagtg gagcgtgatc tactctgggt tccagacacc 1320
tgtcactcac ccagtggtca aagggggagt gcgaaaccag aatgacaacc gggccgaggc 1380
cttctgtaca tcctacggct tctttcccgg ggagatcaat attactttta tccattacgg 1440
caacaaggcc cccgacgatt ctgagcctca gtgcaatccc ctgctgccta ccttcgatgg 1500
cacatttcac caggggtgct acgtcgctat cttctgcaat cagaactata cttgccgggt 1560
gacccatggg aactggactg tggaaatccc aatttcagtc accagccccg acgattcaag 1620
ctccggagag gtgccagatc accccaccgc aaataagaga tacaacacca tgacaatctc 1680
tagtgtgctg ctggccctgc tgctgtgcgc actgctgttc gcttttctgc attacttcac 1740
aactctgaag cagtatctgc ggaacctggc atttgcctgg cggtacagaa aagtgagatc 1800
aagctgactg tgccttctag ttgccagcca tctgttgttt gcccctcccc cgtgccttcc 1860
ttgaccctgg aaggtgccac tcccactgtc ctttcctaat aaaatgagga aattgcatcg 1920
cattgtctga gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg 1980
gaggattggg aagacaatag caggcatgct ggggatgcgg tgggctctat gtctctttct 2040
ggcctggagg ctatccagcg tgagtctctc ctaccctccc gctctggtcc ttcctctccc 2100
gctctgcacc ctctgtggcc ctcgctgtgc tctctcgctc cgtgacttcc cttctccaag 2160
ttctccttgg tggcccgccg tggggctagt ccagggctgg atctcgggga agcggcgggg 2220
tggcctggga gtggggaagg gggtgcgcac ccgggacgcg cgctacttgc ccctttcggc 2280
ggggagcagg ggagaccttt ggcctacggc gacgggaggg tcgggacaaa g 2331
<210> 76
<211> 2531
<212> DNA
<213> artificial sequence
<220>
<223> UL18Trimer matrix _HLAG peptide inserted at the B2m locus
<400> 76
cacttagcat ctctggggcc agtctgcaaa gcgagggggc agccttaatg tgcctccagc 60
ctgaagtcct agaatgagcg cccggtgtcc caagctgggg cgcgcacccc agatcggagg 120
gcgccgatgt acagacagca aactcaccca gtctagtgca tgccttctta aacatcacga 180
gactctaaga aaaggaaact gaaaacggga aagtccctct ctctaacctg gcactgcgtc 240
gctggcttgg agacaggtga cggtccctgc gggccttgtc ctgattggct gggcacgcgt 300
ttaatataag tggaggcgtc gcgctggcgg gcattcctga agctgacagc attcgggccg 360
agatgtctcg ctccgtggcc ttagctgtgc tcgcgctact ctctcttagc ggcctcgaag 420
ctgttatggc tccgcggact ttattcttag gtggtggcgg atccggtggt ggcggttctg 480
gtggtggcgg ctccatccag cgtacgccca aaattcaagt ctacagccga catcctgcag 540
agaacggcaa atctaatttc ctgaactgct atgtatcagg ctttcaccct agcgatatag 600
aagtggacct gctgaaaaac ggagagagga tagaaaaggt cgaacacagc gacctctcct 660
tttccaagga ctggagcttt tatcttctgt attatactga atttacaccc acggaaaaag 720
atgagtatgc gtgccgagta aaccacgtca cgctgtcaca gcccaaaata gtaaaatggg 780
atcgcgacat gggtggtggc ggttctggtg gtggcggtag tggcggcgga ggaagcggtg 840
gtggcggttc cggatctatg cacgtgctga gatacggata taccggcatc ttcgacgata 900
catcccatat gactctgacc gtggtcggga tttttgacgg acagcacttc tttacatacc 960
atgtgaacag ctccgataag gcttctagtc gagcaaatgg caccatctca tggatggcca 1020
acgtgagcgc agcctacccc acatatctgg acggagaacg cgctaaaggc gatctgatct 1080
tcaatcagac cgagcagaac ctgctggagc tggaaattgc tctggggtac aggtctcaga 1140
gtgtcctgac atggactcac gaatgtaata ccacagagaa cgggagcttc gtggcaggat 1200
atgagggctt tgggtgggac ggagaaacac tgatggagct gaaggataat ctgactctgt 1260
ggaccggccc taactacgaa atcagctggc tgaagcagaa caagacttac atcgacggaa 1320
agatcaaaaa catcagcgag ggcgatacta ccatccagcg caattacctg aagggcaact 1380
gcacccagtg gagcgtgatc tactctgggt tccagacacc tgtcactcac ccagtggtca 1440
aagggggagt gcgaaaccag aatgacaacc gggccgaggc cttctgtaca tcctacggct 1500
tctttcccgg ggagatcaat attactttta tccattacgg caacaaggcc cccgacgatt 1560
ctgagcctca gtgcaatccc ctgctgccta ccttcgatgg cacatttcac caggggtgct 1620
acgtcgctat cttctgcaat cagaactata cttgccgggt gacccatggg aactggactg 1680
tggaaatccc aatttcagtc accagccccg acgattcaag ctccggagag gtgccagatc 1740
accccaccgc aaataagaga tacaacacca tgacaatctc tagtgtgctg ctggccctgc 1800
tgctgtgcgc actgctgttc gcttttctgc attacttcac aactctgaag cagtatctgc 1860
ggaacctggc atttgcctgg cggtacagaa aagtgagatc aagctgactg tgccttctag 1920
ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 1980
tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 2040
ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag 2100
caggcatgct ggggatgcgg tgggctctat gtctctttct ggcctggagg ctatccagcg 2160
tgagtctctc ctaccctccc gctctggtcc ttcctctccc gctctgcacc ctctgtggcc 2220
ctcgctgtgc tctctcgctc cgtgacttcc cttctccaag ttctccttgg tggcccgccg 2280
tggggctagt ccagggctgg atctcgggga agcggcgggg tggcctggga gtggggaagg 2340
gggtgcgcac ccgggacgcg cgctacttgc ccctttcggc ggggagcagg ggagaccttt 2400
ggcctacggc gacgggaggg tcgggacaaa gtttagggcg tcgataagcg tcagagcgcc 2460
gaggttgggg gagggtttct cttccgctct ttcgcggggc ctctggctcc cccagcgcag 2520
ctggagtggg g 2531
<210> 77
<211> 2331
<212> DNA
<213> artificial sequence
<220>
<223> UL18Trimer matrix _HLAG peptide
<400> 77
cgcgcacccc agatcggagg gcgccgatgt acagacagca aactcaccca gtctagtgca 60
tgccttctta aacatcacga gactctaaga aaaggaaact gaaaacggga aagtccctct 120
ctctaacctg gcactgcgtc gctggcttgg agacaggtga cggtccctgc gggccttgtc 180
ctgattggct gggcacgcgt ttaatataag tggaggcgtc gcgctggcgg gcattcctga 240
agctgacagc attcgggccg agatgtctcg ctccgtggcc ttagctgtgc tcgcgctact 300
ctctcttagc ggcctcgaag ctgttatggc tccgcggact ttattcttag gtggtggcgg 360
atccggtggt ggcggttctg gtggtggcgg ctccatccag cgtacgccca aaattcaagt 420
ctacagccga catcctgcag agaacggcaa atctaatttc ctgaactgct atgtatcagg 480
ctttcaccct agcgatatag aagtggacct gctgaaaaac ggagagagga tagaaaaggt 540
cgaacacagc gacctctcct tttccaagga ctggagcttt tatcttctgt attatactga 600
atttacaccc acggaaaaag atgagtatgc gtgccgagta aaccacgtca cgctgtcaca 660
gcccaaaata gtaaaatggg atcgcgacat gggtggtggc ggttctggtg gtggcggtag 720
tggcggcgga ggaagcggtg gtggcggttc cggatctatg cacgtgctga gatacggata 780
taccggcatc ttcgacgata catcccatat gactctgacc gtggtcggga tttttgacgg 840
acagcacttc tttacatacc atgtgaacag ctccgataag gcttctagtc gagcaaatgg 900
caccatctca tggatggcca acgtgagcgc agcctacccc acatatctgg acggagaacg 960
cgctaaaggc gatctgatct tcaatcagac cgagcagaac ctgctggagc tggaaattgc 1020
tctggggtac aggtctcaga gtgtcctgac atggactcac gaatgtaata ccacagagaa 1080
cgggagcttc gtggcaggat atgagggctt tgggtgggac ggagaaacac tgatggagct 1140
gaaggataat ctgactctgt ggaccggccc taactacgaa atcagctggc tgaagcagaa 1200
caagacttac atcgacggaa agatcaaaaa catcagcgag ggcgatacta ccatccagcg 1260
caattacctg aagggcaact gcacccagtg gagcgtgatc tactctgggt tccagacacc 1320
tgtcactcac ccagtggtca aagggggagt gcgaaaccag aatgacaacc gggccgaggc 1380
cttctgtaca tcctacggct tctttcccgg ggagatcaat attactttta tccattacgg 1440
caacaaggcc cccgacgatt ctgagcctca gtgcaatccc ctgctgccta ccttcgatgg 1500
cacatttcac caggggtgct acgtcgctat cttctgcaat cagaactata cttgccgggt 1560
gacccatggg aactggactg tggaaatccc aatttcagtc accagccccg acgattcaag 1620
ctccggagag gtgccagatc accccaccgc aaataagaga tacaacacca tgacaatctc 1680
tagtgtgctg ctggccctgc tgctgtgcgc actgctgttc gcttttctgc attacttcac 1740
aactctgaag cagtatctgc ggaacctggc atttgcctgg cggtacagaa aagtgagatc 1800
aagctgactg tgccttctag ttgccagcca tctgttgttt gcccctcccc cgtgccttcc 1860
ttgaccctgg aaggtgccac tcccactgtc ctttcctaat aaaatgagga aattgcatcg 1920
cattgtctga gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg 1980
gaggattggg aagacaatag caggcatgct ggggatgcgg tgggctctat gtctctttct 2040
ggcctggagg ctatccagcg tgagtctctc ctaccctccc gctctggtcc ttcctctccc 2100
gctctgcacc ctctgtggcc ctcgctgtgc tctctcgctc cgtgacttcc cttctccaag 2160
ttctccttgg tggcccgccg tggggctagt ccagggctgg atctcgggga agcggcgggg 2220
tggcctggga gtggggaagg gggtgcgcac ccgggacgcg cgctacttgc ccctttcggc 2280
ggggagcagg ggagaccttt ggcctacggc gacgggaggg tcgggacaaa g 2331
<210> 78
<211> 47
<212> DNA
<213> artificial sequence
<220>
<223> TALEN target B2m1
<400> 78
tccgtggcct tagctgtgct cgcgctactc tctctttctg gcctgga 47
<210> 79
<211> 47
<212> DNA
<213> artificial sequence
<220>
<223> TALEN target B2m2
<400> 79
ttagctgtgc tcgcgctact ctctctttct ggcctggagg ctatcca 47
<210> 80
<211> 936
<212> PRT
<213> artificial sequence
<220>
<223> pCLS31134 right TALEN B2m1
<400> 80
Met Gly Asp Pro Lys Lys Lys Arg Lys Val Ile Asp Tyr Pro Tyr Asp
1 5 10 15
Val Pro Asp Tyr Ala Ile Asp Ile Ala Asp Leu Arg Thr Leu Gly Tyr
20 25 30
Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys Val Arg Ser Thr Val
35 40 45
Ala Gln His His Glu Ala Leu Val Gly His Gly Phe Thr His Ala His
50 55 60
Ile Val Ala Leu Ser Gln His Pro Ala Ala Leu Gly Thr Val Ala Val
65 70 75 80
Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro Glu Ala Thr His Glu Ala
85 90 95
Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala Arg Ala Leu Glu Ala
100 105 110
Leu Leu Thr Val Ala Gly Glu Leu Arg Gly Pro Pro Leu Gln Leu Asp
115 120 125
Thr Gly Gln Leu Leu Lys Ile Ala Lys Arg Gly Gly Val Thr Ala Val
130 135 140
Glu Ala Val His Ala Trp Arg Asn Ala Leu Thr Gly Ala Pro Leu Asn
145 150 155 160
Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys
165 170 175
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
180 185 190
His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly
195 200 205
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
210 215 220
Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn
225 230 235 240
Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
245 250 255
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
260 265 270
Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
275 280 285
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
290 295 300
Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
305 310 315 320
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
325 330 335
Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val
340 345 350
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
355 360 365
Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu
370 375 380
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
385 390 395 400
Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala
405 410 415
Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly
420 425 430
Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys
435 440 445
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
450 455 460
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly
465 470 475 480
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
485 490 495
Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn
500 505 510
Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val
515 520 525
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
530 535 540
Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
545 550 555 560
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala
565 570 575
Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
580 585 590
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
595 600 605
Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val
610 615 620
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln
625 630 635 640
Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu
645 650 655
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
660 665 670
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Arg Pro Ala
675 680 685
Leu Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala
690 695 700
Ala Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys Leu Gly Gly Arg
705 710 715 720
Pro Ala Leu Asp Ala Val Lys Lys Gly Leu Gly Asp Pro Ile Ser Arg
725 730 735
Ser Gln Leu Val Lys Ser Glu Leu Glu Glu Lys Lys Ser Glu Leu Arg
740 745 750
His Lys Leu Lys Tyr Val Pro His Glu Tyr Ile Glu Leu Ile Glu Ile
755 760 765
Ala Arg Asn Ser Thr Gln Asp Arg Ile Leu Glu Met Lys Val Met Glu
770 775 780
Phe Phe Met Lys Val Tyr Gly Tyr Arg Gly Lys His Leu Gly Gly Ser
785 790 795 800
Arg Lys Pro Asp Gly Ala Ile Tyr Thr Val Gly Ser Pro Ile Asp Tyr
805 810 815
Gly Val Ile Val Asp Thr Lys Ala Tyr Ser Gly Gly Tyr Asn Leu Pro
820 825 830
Ile Gly Gln Ala Asp Glu Met Gln Arg Tyr Val Glu Glu Asn Gln Thr
835 840 845
Arg Asn Lys His Ile Asn Pro Asn Glu Trp Trp Lys Val Tyr Pro Ser
850 855 860
Ser Val Thr Glu Phe Lys Phe Leu Phe Val Ser Gly His Phe Lys Gly
865 870 875 880
Asn Tyr Lys Ala Gln Leu Thr Arg Leu Asn His Ile Thr Asn Cys Asn
885 890 895
Gly Ala Val Leu Ser Val Glu Glu Leu Leu Ile Gly Gly Glu Met Ile
900 905 910
Lys Ala Gly Thr Leu Thr Leu Glu Glu Val Arg Arg Lys Phe Asn Asn
915 920 925
Gly Glu Ile Asn Phe Ala Ala Asp
930 935
<210> 81
<211> 936
<212> PRT
<213> artificial sequence
<220>
<223> pCLS31135 left TALEN B2m1
<400> 81
Met Gly Asp Pro Lys Lys Lys Arg Lys Val Ile Asp Tyr Pro Tyr Asp
1 5 10 15
Val Pro Asp Tyr Ala Ile Asp Ile Ala Asp Leu Arg Thr Leu Gly Tyr
20 25 30
Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys Val Arg Ser Thr Val
35 40 45
Ala Gln His His Glu Ala Leu Val Gly His Gly Phe Thr His Ala His
50 55 60
Ile Val Ala Leu Ser Gln His Pro Ala Ala Leu Gly Thr Val Ala Val
65 70 75 80
Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro Glu Ala Thr His Glu Ala
85 90 95
Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala Arg Ala Leu Glu Ala
100 105 110
Leu Leu Thr Val Ala Gly Glu Leu Arg Gly Pro Pro Leu Gln Leu Asp
115 120 125
Thr Gly Gln Leu Leu Lys Ile Ala Lys Arg Gly Gly Val Thr Ala Val
130 135 140
Glu Ala Val His Ala Trp Arg Asn Ala Leu Thr Gly Ala Pro Leu Asn
145 150 155 160
Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys
165 170 175
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
180 185 190
His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly
195 200 205
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
210 215 220
Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn
225 230 235 240
Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val
245 250 255
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
260 265 270
Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
275 280 285
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
290 295 300
Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
305 310 315 320
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val
325 330 335
Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val
340 345 350
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
355 360 365
Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu
370 375 380
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
385 390 395 400
Pro Glu Gln Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala
405 410 415
Leu Glu Thr Val Gln Ala Leu Leu Pro Val Leu Cys Gln Ala His Gly
420 425 430
Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys
435 440 445
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
450 455 460
His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn Ile Gly
465 470 475 480
Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val Leu Cys
485 490 495
Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn
500 505 510
Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val
515 520 525
Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala
530 535 540
Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu
545 550 555 560
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
565 570 575
Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
580 585 590
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val
595 600 605
Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val
610 615 620
Gln Ala Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln
625 630 635 640
Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu
645 650 655
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
660 665 670
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Arg Pro Ala
675 680 685
Leu Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala
690 695 700
Ala Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys Leu Gly Gly Arg
705 710 715 720
Pro Ala Leu Asp Ala Val Lys Lys Gly Leu Gly Asp Pro Ile Ser Arg
725 730 735
Ser Gln Leu Val Lys Ser Glu Leu Glu Glu Lys Lys Ser Glu Leu Arg
740 745 750
His Lys Leu Lys Tyr Val Pro His Glu Tyr Ile Glu Leu Ile Glu Ile
755 760 765
Ala Arg Asn Ser Thr Gln Asp Arg Ile Leu Glu Met Lys Val Met Glu
770 775 780
Phe Phe Met Lys Val Tyr Gly Tyr Arg Gly Lys His Leu Gly Gly Ser
785 790 795 800
Arg Lys Pro Asp Gly Ala Ile Tyr Thr Val Gly Ser Pro Ile Asp Tyr
805 810 815
Gly Val Ile Val Asp Thr Lys Ala Tyr Ser Gly Gly Tyr Asn Leu Pro
820 825 830
Ile Gly Gln Ala Asp Glu Met Gln Arg Tyr Val Glu Glu Asn Gln Thr
835 840 845
Arg Asn Lys His Ile Asn Pro Asn Glu Trp Trp Lys Val Tyr Pro Ser
850 855 860
Ser Val Thr Glu Phe Lys Phe Leu Phe Val Ser Gly His Phe Lys Gly
865 870 875 880
Asn Tyr Lys Ala Gln Leu Thr Arg Leu Asn His Ile Thr Asn Cys Asn
885 890 895
Gly Ala Val Leu Ser Val Glu Glu Leu Leu Ile Gly Gly Glu Met Ile
900 905 910
Lys Ala Gly Thr Leu Thr Leu Glu Glu Val Arg Arg Lys Phe Asn Asn
915 920 925
Gly Glu Ile Asn Phe Ala Ala Asp
930 935
<210> 82
<211> 936
<212> PRT
<213> artificial sequence
<220>
<223> pCLS31136 right TALEN B2m2
<400> 82
Met Gly Asp Pro Lys Lys Lys Arg Lys Val Ile Asp Tyr Pro Tyr Asp
1 5 10 15
Val Pro Asp Tyr Ala Ile Asp Ile Ala Asp Leu Arg Thr Leu Gly Tyr
20 25 30
Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys Val Arg Ser Thr Val
35 40 45
Ala Gln His His Glu Ala Leu Val Gly His Gly Phe Thr His Ala His
50 55 60
Ile Val Ala Leu Ser Gln His Pro Ala Ala Leu Gly Thr Val Ala Val
65 70 75 80
Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro Glu Ala Thr His Glu Ala
85 90 95
Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala Arg Ala Leu Glu Ala
100 105 110
Leu Leu Thr Val Ala Gly Glu Leu Arg Gly Pro Pro Leu Gln Leu Asp
115 120 125
Thr Gly Gln Leu Leu Lys Ile Ala Lys Arg Gly Gly Val Thr Ala Val
130 135 140
Glu Ala Val His Ala Trp Arg Asn Ala Leu Thr Gly Ala Pro Leu Asn
145 150 155 160
Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys
165 170 175
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
180 185 190
His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn Ile Gly
195 200 205
Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val Leu Cys
210 215 220
Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn
225 230 235 240
Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
245 250 255
Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala
260 265 270
Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
275 280 285
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
290 295 300
Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
305 310 315 320
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
325 330 335
Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val
340 345 350
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln
355 360 365
Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu
370 375 380
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
385 390 395 400
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala
405 410 415
Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly
420 425 430
Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys
435 440 445
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
450 455 460
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly
465 470 475 480
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
485 490 495
Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His
500 505 510
Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
515 520 525
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
530 535 540
Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
545 550 555 560
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala
565 570 575
Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
580 585 590
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
595 600 605
Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val
610 615 620
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
625 630 635 640
Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu
645 650 655
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
660 665 670
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Arg Pro Ala
675 680 685
Leu Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala
690 695 700
Ala Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys Leu Gly Gly Arg
705 710 715 720
Pro Ala Leu Asp Ala Val Lys Lys Gly Leu Gly Asp Pro Ile Ser Arg
725 730 735
Ser Gln Leu Val Lys Ser Glu Leu Glu Glu Lys Lys Ser Glu Leu Arg
740 745 750
His Lys Leu Lys Tyr Val Pro His Glu Tyr Ile Glu Leu Ile Glu Ile
755 760 765
Ala Arg Asn Ser Thr Gln Asp Arg Ile Leu Glu Met Lys Val Met Glu
770 775 780
Phe Phe Met Lys Val Tyr Gly Tyr Arg Gly Lys His Leu Gly Gly Ser
785 790 795 800
Arg Lys Pro Asp Gly Ala Ile Tyr Thr Val Gly Ser Pro Ile Asp Tyr
805 810 815
Gly Val Ile Val Asp Thr Lys Ala Tyr Ser Gly Gly Tyr Asn Leu Pro
820 825 830
Ile Gly Gln Ala Asp Glu Met Gln Arg Tyr Val Glu Glu Asn Gln Thr
835 840 845
Arg Asn Lys His Ile Asn Pro Asn Glu Trp Trp Lys Val Tyr Pro Ser
850 855 860
Ser Val Thr Glu Phe Lys Phe Leu Phe Val Ser Gly His Phe Lys Gly
865 870 875 880
Asn Tyr Lys Ala Gln Leu Thr Arg Leu Asn His Ile Thr Asn Cys Asn
885 890 895
Gly Ala Val Leu Ser Val Glu Glu Leu Leu Ile Gly Gly Glu Met Ile
900 905 910
Lys Ala Gly Thr Leu Thr Leu Glu Glu Val Arg Arg Lys Phe Asn Asn
915 920 925
Gly Glu Ile Asn Phe Ala Ala Asp
930 935
<210> 83
<211> 936
<212> PRT
<213> artificial sequence
<220>
<223> pCLS31137 left TALEN B2m2
<400> 83
Met Gly Asp Pro Lys Lys Lys Arg Lys Val Ile Asp Tyr Pro Tyr Asp
1 5 10 15
Val Pro Asp Tyr Ala Ile Asp Ile Ala Asp Leu Arg Thr Leu Gly Tyr
20 25 30
Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys Val Arg Ser Thr Val
35 40 45
Ala Gln His His Glu Ala Leu Val Gly His Gly Phe Thr His Ala His
50 55 60
Ile Val Ala Leu Ser Gln His Pro Ala Ala Leu Gly Thr Val Ala Val
65 70 75 80
Lys Tyr Gln Asp Met Ile Ala Ala Leu Pro Glu Ala Thr His Glu Ala
85 90 95
Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala Arg Ala Leu Glu Ala
100 105 110
Leu Leu Thr Val Ala Gly Glu Leu Arg Gly Pro Pro Leu Gln Leu Asp
115 120 125
Thr Gly Gln Leu Leu Lys Ile Ala Lys Arg Gly Gly Val Thr Ala Val
130 135 140
Glu Ala Val His Ala Trp Arg Asn Ala Leu Thr Gly Ala Pro Leu Asn
145 150 155 160
Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys
165 170 175
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
180 185 190
His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Asn Gly
195 200 205
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
210 215 220
Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser Asn
225 230 235 240
Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu Pro Val
245 250 255
Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala Ile Ala
260 265 270
Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu
275 280 285
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala
290 295 300
Ile Ala Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala
305 310 315 320
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
325 330 335
Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val
340 345 350
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
355 360 365
Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu
370 375 380
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
385 390 395 400
Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala
405 410 415
Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly
420 425 430
Leu Thr Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys
435 440 445
Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala
450 455 460
His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His Asp Gly
465 470 475 480
Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys
485 490 495
Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala Ser His
500 505 510
Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val
515 520 525
Leu Cys Gln Ala His Gly Leu Thr Pro Glu Gln Val Val Ala Ile Ala
530 535 540
Ser Asn Ile Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Ala Leu Leu
545 550 555 560
Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val Val Ala
565 570 575
Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg
580 585 590
Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Gln Gln Val
595 600 605
Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val
610 615 620
Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr Pro Glu
625 630 635 640
Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu
645 650 655
Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Ala His Gly Leu Thr
660 665 670
Pro Gln Gln Val Val Ala Ile Ala Ser Asn Gly Gly Gly Arg Pro Ala
675 680 685
Leu Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala
690 695 700
Ala Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys Leu Gly Gly Arg
705 710 715 720
Pro Ala Leu Asp Ala Val Lys Lys Gly Leu Gly Asp Pro Ile Ser Arg
725 730 735
Ser Gln Leu Val Lys Ser Glu Leu Glu Glu Lys Lys Ser Glu Leu Arg
740 745 750
His Lys Leu Lys Tyr Val Pro His Glu Tyr Ile Glu Leu Ile Glu Ile
755 760 765
Ala Arg Asn Ser Thr Gln Asp Arg Ile Leu Glu Met Lys Val Met Glu
770 775 780
Phe Phe Met Lys Val Tyr Gly Tyr Arg Gly Lys His Leu Gly Gly Ser
785 790 795 800
Arg Lys Pro Asp Gly Ala Ile Tyr Thr Val Gly Ser Pro Ile Asp Tyr
805 810 815
Gly Val Ile Val Asp Thr Lys Ala Tyr Ser Gly Gly Tyr Asn Leu Pro
820 825 830
Ile Gly Gln Ala Asp Glu Met Gln Arg Tyr Val Glu Glu Asn Gln Thr
835 840 845
Arg Asn Lys His Ile Asn Pro Asn Glu Trp Trp Lys Val Tyr Pro Ser
850 855 860
Ser Val Thr Glu Phe Lys Phe Leu Phe Val Ser Gly His Phe Lys Gly
865 870 875 880
Asn Tyr Lys Ala Gln Leu Thr Arg Leu Asn His Ile Thr Asn Cys Asn
885 890 895
Gly Ala Val Leu Ser Val Glu Glu Leu Leu Ile Gly Gly Glu Met Ile
900 905 910
Lys Ala Gly Thr Leu Thr Leu Glu Glu Val Arg Arg Lys Phe Asn Asn
915 920 925
Gly Glu Ile Asn Phe Ala Ala Asp
930 935
<210> 84
<211> 338
<212> PRT
<213> artificial sequence
<220>
<223> HLAG1
<400> 84
Met Val Val Met Ala Pro Arg Thr Leu Phe Leu Leu Leu Ser Gly Ala
1 5 10 15
Leu Thr Leu Thr Glu Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe
20 25 30
Ser Ala Ala Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala
35 40 45
Met Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ser
50 55 60
Ala Cys Pro Arg Met Glu Pro Arg Ala Pro Trp Val Glu Gln Glu Gly
65 70 75 80
Pro Glu Tyr Trp Glu Glu Glu Thr Arg Asn Thr Lys Ala His Ala Gln
85 90 95
Thr Asp Arg Met Asn Leu Gln Thr Leu Arg Gly Tyr Tyr Asn Gln Ser
100 105 110
Glu Ala Ser Ser His Thr Leu Gln Trp Met Ile Gly Cys Asp Leu Gly
115 120 125
Ser Asp Gly Arg Leu Leu Arg Gly Tyr Glu Gln Tyr Ala Tyr Asp Gly
130 135 140
Lys Asp Tyr Leu Ala Leu Asn Glu Asp Leu Arg Ser Trp Thr Ala Ala
145 150 155 160
Asp Thr Ala Ala Gln Ile Ser Lys Arg Lys Cys Glu Ala Ala Asn Val
165 170 175
Ala Glu Gln Arg Arg Ala Tyr Leu Glu Gly Thr Cys Val Glu Trp Leu
180 185 190
His Arg Tyr Leu Glu Asn Gly Lys Glu Met Leu Gln Arg Ala Asp Pro
195 200 205
Pro Lys Thr His Val Thr His His Pro Val Phe Asp Tyr Glu Ala Thr
210 215 220
Leu Arg Cys Trp Ala Leu Gly Phe Tyr Pro Ala Glu Ile Ile Leu Thr
225 230 235 240
Trp Gln Arg Asp Gly Glu Asp Gln Thr Gln Asp Val Glu Leu Val Glu
245 250 255
Thr Arg Pro Ala Gly Asp Gly Thr Phe Gln Lys Trp Ala Ala Val Val
260 265 270
Val Pro Ser Gly Glu Glu Gln Arg Tyr Thr Cys His Val Gln His Glu
275 280 285
Gly Leu Pro Glu Pro Leu Met Leu Arg Trp Lys Gln Ser Ser Leu Pro
290 295 300
Thr Ile Pro Ile Met Gly Ile Val Ala Gly Leu Val Val Leu Ala Ala
305 310 315 320
Val Val Thr Gly Ala Ala Val Ala Ala Val Leu Trp Arg Lys Lys Ser
325 330 335
Ser Asp
<210> 85
<211> 246
<212> PRT
<213> artificial sequence
<220>
<223> HLAG2
<400> 85
Met Val Val Met Ala Pro Arg Thr Leu Phe Leu Leu Leu Ser Gly Ala
1 5 10 15
Leu Thr Leu Thr Glu Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe
20 25 30
Ser Ala Ala Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala
35 40 45
Met Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ser
50 55 60
Ala Cys Pro Arg Met Glu Pro Arg Ala Pro Trp Val Glu Gln Glu Gly
65 70 75 80
Pro Glu Tyr Trp Glu Glu Glu Thr Arg Asn Thr Lys Ala His Ala Gln
85 90 95
Thr Asp Arg Met Asn Leu Gln Thr Leu Arg Gly Tyr Tyr Asn Gln Ser
100 105 110
Glu Ala Lys Pro Pro Lys Thr His Val Thr His His Pro Val Phe Asp
115 120 125
Tyr Glu Ala Thr Leu Arg Cys Trp Ala Leu Gly Phe Tyr Pro Ala Glu
130 135 140
Ile Ile Leu Thr Trp Gln Arg Asp Gly Glu Asp Gln Thr Gln Asp Val
145 150 155 160
Glu Leu Val Glu Thr Arg Pro Ala Gly Asp Gly Thr Phe Gln Lys Trp
165 170 175
Ala Ala Val Val Val Pro Ser Gly Glu Glu Gln Arg Tyr Thr Cys His
180 185 190
Val Gln His Glu Gly Leu Pro Glu Pro Leu Met Leu Arg Trp Lys Gln
195 200 205
Ser Ser Leu Pro Thr Ile Pro Ile Met Gly Ile Val Ala Gly Leu Val
210 215 220
Val Leu Ala Ala Val Val Thr Gly Ala Ala Val Ala Ala Val Leu Trp
225 230 235 240
Arg Lys Lys Ser Ser Asp
245
<210> 86
<211> 154
<212> PRT
<213> artificial sequence
<220>
<223> HLAG3
<400> 86
Met Val Val Met Ala Pro Arg Thr Leu Phe Leu Leu Leu Ser Gly Ala
1 5 10 15
Leu Thr Leu Thr Glu Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe
20 25 30
Ser Ala Ala Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala
35 40 45
Met Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ser
50 55 60
Ala Cys Pro Arg Met Glu Pro Arg Ala Pro Trp Val Glu Gln Glu Gly
65 70 75 80
Pro Glu Tyr Trp Glu Glu Glu Thr Arg Asn Thr Lys Ala His Ala Gln
85 90 95
Thr Asp Arg Met Asn Leu Gln Thr Leu Arg Gly Tyr Tyr Asn Gln Ser
100 105 110
Glu Ala Lys Gln Ser Ser Leu Pro Thr Ile Pro Ile Met Gly Ile Val
115 120 125
Ala Gly Leu Val Val Leu Ala Ala Val Val Thr Gly Ala Ala Val Ala
130 135 140
Ala Val Leu Trp Arg Lys Lys Ser Ser Asp
145 150
<210> 87
<211> 246
<212> PRT
<213> artificial sequence
<220>
<223> HLAG4
<400> 87
Met Val Val Met Ala Pro Arg Thr Leu Phe Leu Leu Leu Ser Gly Ala
1 5 10 15
Leu Thr Leu Thr Glu Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe
20 25 30
Ser Ala Ala Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala
35 40 45
Met Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ser
50 55 60
Ala Cys Pro Arg Met Glu Pro Arg Ala Pro Trp Val Glu Gln Glu Gly
65 70 75 80
Pro Glu Tyr Trp Glu Glu Glu Thr Arg Asn Thr Lys Ala His Ala Gln
85 90 95
Thr Asp Arg Met Asn Leu Gln Thr Leu Arg Gly Tyr Tyr Asn Gln Ser
100 105 110
Glu Ala Ser Ser His Thr Leu Gln Trp Met Ile Gly Cys Asp Leu Gly
115 120 125
Ser Asp Gly Arg Leu Leu Arg Gly Tyr Glu Gln Tyr Ala Tyr Asp Gly
130 135 140
Lys Asp Tyr Leu Ala Leu Asn Glu Asp Leu Arg Ser Trp Thr Ala Ala
145 150 155 160
Asp Thr Ala Ala Gln Ile Ser Lys Arg Lys Cys Glu Ala Ala Asn Val
165 170 175
Ala Glu Gln Arg Arg Ala Tyr Leu Glu Gly Thr Cys Val Glu Trp Leu
180 185 190
His Arg Tyr Leu Glu Asn Gly Lys Glu Met Leu Gln Arg Ala Lys Gln
195 200 205
Ser Ser Leu Pro Thr Ile Pro Ile Met Gly Ile Val Ala Gly Leu Val
210 215 220
Val Leu Ala Ala Val Val Thr Gly Ala Ala Val Ala Ala Val Leu Trp
225 230 235 240
Arg Lys Lys Ser Ser Asp
245
<210> 88
<211> 319
<212> PRT
<213> artificial sequence
<220>
<223> HLAG5
<400> 88
Met Val Val Met Ala Pro Arg Thr Leu Phe Leu Leu Leu Ser Gly Ala
1 5 10 15
Leu Thr Leu Thr Glu Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe
20 25 30
Ser Ala Ala Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala
35 40 45
Met Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ser
50 55 60
Ala Cys Pro Arg Met Glu Pro Arg Ala Pro Trp Val Glu Gln Glu Gly
65 70 75 80
Pro Glu Tyr Trp Glu Glu Glu Thr Arg Asn Thr Lys Ala His Ala Gln
85 90 95
Thr Asp Arg Met Asn Leu Gln Thr Leu Arg Gly Tyr Tyr Asn Gln Ser
100 105 110
Glu Ala Ser Ser His Thr Leu Gln Trp Met Ile Gly Cys Asp Leu Gly
115 120 125
Ser Asp Gly Arg Leu Leu Arg Gly Tyr Glu Gln Tyr Ala Tyr Asp Gly
130 135 140
Lys Asp Tyr Leu Ala Leu Asn Glu Asp Leu Arg Ser Trp Thr Ala Ala
145 150 155 160
Asp Thr Ala Ala Gln Ile Ser Lys Arg Lys Cys Glu Ala Ala Asn Val
165 170 175
Ala Glu Gln Arg Arg Ala Tyr Leu Glu Gly Thr Cys Val Glu Trp Leu
180 185 190
His Arg Tyr Leu Glu Asn Gly Lys Glu Met Leu Gln Arg Ala Asp Pro
195 200 205
Pro Lys Thr His Val Thr His His Pro Val Phe Asp Tyr Glu Ala Thr
210 215 220
Leu Arg Cys Trp Ala Leu Gly Phe Tyr Pro Ala Glu Ile Ile Leu Thr
225 230 235 240
Trp Gln Arg Asp Gly Glu Asp Gln Thr Gln Asp Val Glu Leu Val Glu
245 250 255
Thr Arg Pro Ala Gly Asp Gly Thr Phe Gln Lys Trp Ala Ala Val Val
260 265 270
Val Pro Ser Gly Glu Glu Gln Arg Tyr Thr Cys His Val Gln His Glu
275 280 285
Gly Leu Pro Glu Pro Leu Met Leu Arg Trp Ser Lys Glu Gly Asp Gly
290 295 300
Gly Ile Met Ser Val Arg Glu Ser Arg Ser Leu Ser Glu Asp Leu
305 310 315
<210> 89
<211> 227
<212> PRT
<213> artificial sequence
<220>
<223> HLAG6
<400> 89
Met Val Val Met Ala Pro Arg Thr Leu Phe Leu Leu Leu Ser Gly Ala
1 5 10 15
Leu Thr Leu Thr Glu Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe
20 25 30
Ser Ala Ala Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala
35 40 45
Met Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ser
50 55 60
Ala Cys Pro Arg Met Glu Pro Arg Ala Pro Trp Val Glu Gln Glu Gly
65 70 75 80
Pro Glu Tyr Trp Glu Glu Glu Thr Arg Asn Thr Lys Ala His Ala Gln
85 90 95
Thr Asp Arg Met Asn Leu Gln Thr Leu Arg Gly Tyr Tyr Asn Gln Ser
100 105 110
Glu Ala Lys Pro Pro Lys Thr His Val Thr His His Pro Val Phe Asp
115 120 125
Tyr Glu Ala Thr Leu Arg Cys Trp Ala Leu Gly Phe Tyr Pro Ala Glu
130 135 140
Ile Ile Leu Thr Trp Gln Arg Asp Gly Glu Asp Gln Thr Gln Asp Val
145 150 155 160
Glu Leu Val Glu Thr Arg Pro Ala Gly Asp Gly Thr Phe Gln Lys Trp
165 170 175
Ala Ala Val Val Val Pro Ser Gly Glu Glu Gln Arg Tyr Thr Cys His
180 185 190
Val Gln His Glu Gly Leu Pro Glu Pro Leu Met Leu Arg Trp Ser Lys
195 200 205
Glu Gly Asp Gly Gly Ile Met Ser Val Arg Glu Ser Arg Ser Leu Ser
210 215 220
Glu Asp Leu
225
<210> 90
<211> 116
<212> PRT
<213> artificial sequence
<220>
<223> HLAG7
<400> 90
Met Val Val Met Ala Pro Arg Thr Leu Phe Leu Leu Leu Ser Gly Ala
1 5 10 15
Leu Thr Leu Thr Glu Thr Trp Ala Gly Ser His Ser Met Arg Tyr Phe
20 25 30
Ser Ala Ala Val Ser Arg Pro Gly Arg Gly Glu Pro Arg Phe Ile Ala
35 40 45
Met Gly Tyr Val Asp Asp Thr Gln Phe Val Arg Phe Asp Ser Asp Ser
50 55 60
Ala Cys Pro Arg Met Glu Pro Arg Ala Pro Trp Val Glu Gln Glu Gly
65 70 75 80
Pro Glu Tyr Trp Glu Glu Glu Thr Arg Asn Thr Lys Ala His Ala Gln
85 90 95
Thr Asp Arg Met Asn Leu Gln Thr Leu Arg Gly Tyr Tyr Asn Gln Ser
100 105 110
Glu Ala Ser Glu
115
Claims (39)
- 細胞免疫療法用の操作された初代免疫細胞を調製するための方法であって、
T細胞を含む細胞の集団を提供する工程;
該T細胞のある割合中に、
(i)少なくとも1種類のNK細胞阻害物質をコードするように、選択された内在性遺伝子座に組み込まれる外来性ポリヌクレオチド配列を含む、少なくとも1種類の核酸;
(ii)該選択された内在性遺伝子座を特異的に標的とする、少なくとも1種類の配列特異的試薬
を導入する工程
を含み、該外来性ポリヌクレオチド配列が、該内在性遺伝子座中への標的指向遺伝子組込みによって挿入される、前記方法。 - 前記配列特異的試薬がヌクレアーゼである、請求項1に記載の方法。
- 前記標的指向遺伝子組込みが、前記免疫細胞中への相同組換えまたはNHEJによって作動される、請求項1または2に記載の方法。
- 前記外来性ポリヌクレオチド配列が、前記遺伝子座に存在する内在性プロモーターの転写制御下に組み込まれる、請求項1~3のいずれか一項に記載の方法。
- 前記内在性遺伝子座が、MHC I構成要素、例えばβ2mを発現する遺伝子座である、請求項4に記載の方法。
- 前記外来性配列の前記挿入が、前記内在性遺伝子座でのβ2m発現を不活性化する、請求項5に記載の方法。
- 前記内在性プロモーターが、免疫細胞活性化の間に活性を有しているように選択される、請求項1~4のいずれか一項に記載の方法。
- 前記内在性遺伝子座の前記内在性プロモーターが、T細胞活性化に対して応答性であり、例えば表6から選択される1つである、請求項1~7のいずれか一項に記載の方法。
- 前記T細胞がキメラ抗原受容体(CAR)を与えられている、請求項1~8のいずれか一項に記載の方法。
- 前記キメラ抗原受容体(CAR)をコードする外来性配列が、TCR遺伝子座に組み込まれる、請求項9に記載の方法。
- 前記キメラ抗原受容体(CAR)をコードする前記外来性配列が、内在性TCR配列の発現を阻止する、請求項10に記載の方法。
- 前記内在性遺伝子座での前記内在性プロモーターの活性が、前記キメラ抗原受容体(CAR)を通した前記T細胞の活性化に対して応答性である、請求項9~11のいずれか一項に記載の方法。
- 前記特異的エンドヌクレアーゼ試薬が、RNAもしくはDNAガイドエンドヌクレアーゼ、例えばCas9もしくはCpf1、RNAもしくはDNAガイド、TALエンドヌクレアーゼ、Znフィンガーヌクレアーゼ、ホーミングエンドヌクレアーゼ、またはそれらの任意の組み合わせから選択される、請求項1~12のいずれか一項に記載の方法。
- NK阻害物質をコードする前記外来性配列が、非多型性クラスI分子、例えば、HLA-GもしくはHLA-E、またはその重鎖エピトープを含むその断片をコードする配列を好ましくは含む、請求項1~13のいずれか一項に記載の方法。
- 前記外来性配列が、β2m内在性遺伝子座に組み込まれた場合に、その断片のHLA-EまたはHLA-Gとβ2m断片との融合物の発現を結果としてもたらす、請求項5~14のいずれか一項に記載の方法。
- その断片のHLA-EまたはHLA-Gとβ2m断片との前記融合物が、HLA-EまたはHLA-Gの二量体または三量体の発現を結果としてもたらす、請求項15に記載の方法。
- NK阻害物質をコードする前記外来性配列が、ウイルスエバシンまたはそのエピトープを含む断片、例えばUL16(ULBP1とも呼ばれる‐Uniprot参照番号Q9BZM6)由来のものをコードする配列を好ましくは含む、請求項1~13のいずれか一項に記載の方法。
- 前記T細胞が、初代細胞、好ましくはヒト初代T細胞である、請求項1~17のいずれか一項に記載の方法。
- 請求項1~18のいずれか一項に記載の方法によって取得可能である、操作されたT細胞。
- 内在性遺伝子プロモーターの転写制御下に組み込まれている、NK阻害物質をコードする外来性配列を含む、操作されたT細胞。
- 前記内在性遺伝子プロモーターが、表6に列挙される1つの遺伝子座で選択される、請求項19または20のいずれか一項に記載の操作されたT細胞。
- NK阻害物質をコードする前記外来性配列が、β2m遺伝子座に組み込まれている、請求項19~21のいずれか一項に記載の操作されたT細胞。
- 前記T細胞がキメラ抗原受容体を与えられている、請求項19~22のいずれか一項に記載の操作されたT細胞。
- 遺伝子型[TCR]陰性[β2m]陰性を有する、請求項23に記載の操作されたT細胞。
- 前記CARをコードする外来性配列が、TCR遺伝子座に組み込まれている、請求項23または24に記載の操作されたT細胞。
- 前記T細胞が初代細胞である、請求項19~25のいずれか一項に記載の操作されたT細胞。
- がんまたは感染症の処置についてのその使用のための、請求項19~26のいずれか一項に記載の操作されたT細胞。
- 少なくとも30%、好ましくは50%、より好ましくは80%の、請求項19~27のいずれか一項に記載の操作されたT細胞を含む、治療上有効な免疫細胞の集団。
- 少なくとも30%、好ましくは50%、より好ましくは80%の細胞が、ドナー、好ましくは1人の単一ドナーを起源とする、請求項28に記載の治療上有効な免疫細胞の集団。
- 50%超の前記免疫細胞が、TCR陰性T細胞である、請求項29に記載の初代免疫細胞の集団。
- 50%超の前記免疫細胞が、CAR陽性細胞である、請求項28~30のいずれか一項に記載の初代免疫細胞の集団。
- 請求項28~31のいずれか一項に記載の操作された免疫細胞集団を含む、薬学的組成物。
- 以下の工程を含む、その必要がある患者を処置するための方法:
請求項28~32のいずれか一項に記載の操作された初代免疫細胞の集団を調製する工程;
任意で、該操作された初代免疫細胞を精製または選別する工程;
該操作された初代免疫細胞の集団を、該細胞の該患者中への注入時または注入後に活性化する工程。 - 前記患者が、がんについて処置される、請求項33に記載の方法。
- 前記患者が、感染症について処置される、請求項33に記載の方法。
- 少なくとも以下の工程を含む、T細胞において発現可能なNK阻害物質をコードする適切な配列を特定するための方法:
TCRおよびβ2mの発現が両方とも抑えられているおよび/または不活性化されているT細胞を提供する工程;
推定のNK阻害物質をコードする候補配列を、該T細胞における内在性プロモーターの制御下の内在性遺伝子座に組み込む工程;
結果として生じた操作されたT細胞を、NK細胞の存在下で培養する工程。 - 少なくとも以下の工程を含む、T細胞において発現可能なNK阻害物質をコードする適切な配列を特定するための方法:
TCR発現が抑えられているかまたは不活性化されているT細胞を提供する工程;
推定のNK阻害物質をコードする候補配列をβ2m遺伝子座に組み込むことによって、該T細胞においてβ2m発現を不活性化する工程であって、該推定のNK阻害物質の発現が、該β2m遺伝子座の内在性プロモーターの転写制御下に置かれる、工程;
結果として生じた操作されたT細胞を、NK細胞の存在下で培養する工程。 - 前記T細胞にキメラ抗原受容体を与える工程
をさらに含む、請求項36または37に記載の方法。 - 前記結果として生じた操作されたT細胞の生存を、前記候補配列を発現しない同じものと比較する工程;
任意で、NK細胞に対してより耐性である操作された細胞を選択する工程
をさらに含む、請求項36~38のいずれか一項に記載の方法。
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PCT/EP2018/055957 WO2019076486A1 (en) | 2017-10-19 | 2018-03-09 | TARGETED GENE INTEGRATION OF NK INHIBITOR GENES FOR ENHANCED IMMUNE CELL THERAPY |
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