JP2019500887A - キメラタンパク質および遺伝子発現を調節する方法 - Google Patents
キメラタンパク質および遺伝子発現を調節する方法 Download PDFInfo
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Abstract
Description
本出願は、2016年1月11日付で出願された米国仮特許出願第62/277,322号、2016年6月17日付で出願された米国仮特許出願第62/351,522号、および2016年9月26日付で出願された米国仮特許出願第62/399,902号の恩典を主張するものであり、これらの各々は参照によりその全体が本明細書に組み入れられる。
細胞活性の調節は、細胞外リガンド結合ドメインおよび細胞内(例えば、細胞質)シグナル伝達ドメインを含む膜結合受容体へのリガンドの結合を伴いうる。リガンドとリガンド結合ドメインとの間の複合体の形成は、受容体におけるコンフォメーション修飾および/または化学修飾を引き起こし、これが細胞内に伝達されるシグナルを引き起こしうる。いくつかの状況では、受容体の細胞質部分がリン酸化され(例えば、トランスリン酸化および/または自己リン酸化され)、その活性の変化を引き起こす。これらの事象は、二次メッセンジャーおよび/または補因子タンパク質の動員と連動されうる。ある場合には、細胞質部分の変化は、他のタンパク質(例えば、補因子タンパク質および/または他の受容体)への結合をもたらす。これらの他のタンパク質は、活性化され、次に細胞内でさまざまな機能を実行することができる。
上記を考慮して、例えば標的ポリヌクレオチドの発現を調節することにより、遺伝子発現の条件付き調節を行うための代替組成物および方法がかなり必要とされている。1つの局面において、本開示は、細胞内での標的ポリヌクレオチドの発現を調節するためのシステムを提供する。いくつかの態様において、本システムは、(a) 抗原に結合する際に修飾されるキメラ受容体ポリペプチドであって、受容体修飾がコンフォメーション変化または化学修飾を含む、キメラ受容体ポリペプチド; (b) 受容体修飾に応答して受容体に結合するキメラアダプターポリペプチド; (c)切断認識部位に連結されたアクチュエータモエティであって、該切断認識部位の切断の際にアクチュエータモエティが活性化されて標的ポリヌクレオチドと複合体形成する、アクチュエータモエティを含む、遺伝子調整ポリペプチド(GMP); および(d) 切断認識部位に近接している場合に切断認識部位を切断する切断モエティを含み、ここで: (i) GMPがキメラ受容体ポリペプチドの細胞内領域の一部分を形成し、かつ切断モエティがキメラアダプターポリペプチドの一部分を形成する; (ii) GMPがキメラアダプターポリペプチドの一部分を形成し、かつ切断モエティがキメラ受容体ポリペプチドの細胞内領域の一部分を形成する; または (iii) 切断モエティが、受容体修飾に応答してキメラ受容体ポリペプチドに結合する第2アダプターポリペプチドと複合体形成し、かつGMPがキメラアダプターポリペプチドの一部分を形成する。いくつかの態様において、受容体はSEQ ID NO: 39を含まない。
本明細書において言及される全ての刊行物、特許、および特許出願は、各個々の刊行物、特許、または特許出願が、参照により組み入れられるものと具体的かつ個別的に示されているのと同じ程度まで参照により本明細書に組み入れられる。
本明細書において開示するいくつかの方法の実施では、別段の表示がある場合を除き、当技術分野の技能の範囲内にある、従来の免疫学、生化学、化学、分子生物学、微生物学、細胞生物学、ゲノミクスおよび組換えDNAの技法を使用する。例えばSambrook and Green, Molecular Cloning: A Laboratory Manual, 4th Edition(2012)、Current Protocols in Molecular Biology(F. M. Ausubel, et al. eds.)シリーズ、Methods In Enzymology(Academic Press, Inc.)シリーズ、PCR 2: A Practical Approach(M.J. MacPherson, B.D. Hames and G.R. Taylor eds.(1995))、Harlow and Lane, eds.(1988)Antibodies, A Laboratory Manual、およびCulture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th Edition(R.I. Freshney, ed.(2010))を参照されたい。
スフィンゴシン-1-リン酸受容体5(S1PR5)、メラニン凝集ホルモン受容体1(MCHR1)、メラニン凝集ホルモン受容体2(MCHR2)、メラノコルチン1受容体(αメラノサイト刺激ホルモン受容体)(MC1R)、メラノコルチン2受容体(副腎皮質刺激ホルモン)(MC2R)、メラノコルチン3受容体(MC3R)、メラノコルチン4受容体(MC4R)、メラノコルチン5受容体(MC5R)、メラトニン受容体1A(MTNR1A)、メラトニン受容体1B(MTNR1B)、グルタミン酸受容体、代謝調節型1(GRM1)、グルタミン酸受容体、代謝調節型2(GRM2)、グルタミン酸受容体、代謝調節型3(GRM3)、グルタミン酸受容体、代謝調節型4(GRM4)、グルタミン酸受容体、代謝調節型5(GRM5)、グルタミン酸受容体、代謝調節型6(GRM6)、グルタミン酸受容体、代謝調節型7(GRM7)、グルタミン酸受容体、代謝調節型8(GRM8)、モチリン受容体(MLNR)、ニューロメジンU受容体1(NMUR1)、ニューロメジンU受容体2(NMUR2)、ニューロペプチドFF受容体1(NPFFR1)、ニューロペプチドFF受容体2(NPFFR2)、ニューロペプチドS受容体1(NPSR1)、ニューロペプチドB/W受容体1(NPBWR1)、ニューロペプチドB/W受容体2(NPBWR2)、ニューロペプチドY受容体Y1(NPY1R)、ニューロペプチドY受容体Y2(NPY2R)、ニューロペプチドY受容体Y4(NPY4R)、ニューロペプチドY受容体Y5(NPY5R)、ニューロペプチドY受容体Y6(偽遺伝子) (NPY6R)、ニューロテンシン受容体1(高親和性)(NTSR1)、ニューロテンシン受容体2(NTSR2)、オピオイド受容体、δ1(OPRD1)、オピオイド受容体、κ1(OPRK1)、オピオイド受容体、mu 1(OPRM1)、オピエート受容体様1(OPRL1)、ヒポクレチン(オレキシン)受容体1(HCRTR1)、ヒポクレチン(オレキシン)受容体2(HCRTR2)、Gタンパク質共役型受容体107(GPR107)、Gタンパク質共役型受容体137(GPR137)、嗅覚受容体ファミリー51サブファミリーEメンバー1(OR51E1)、膜貫通タンパク質、脂肪細胞関連1(TPRA1)、Gタンパク質共役型受容体143(GPR143)、Gタンパク質共役型受容体157(GPR157)、オキソグルタル酸(α-ケトグルタル酸)受容体1(OXGR1)、プリン作動性受容体P2Y(P2RY1)、プリン作動性受容体P2Y(P2RY2)、ピリミジン作動性受容体P2Y(P2RY4)、ピリミジン作動性受容体P2Y(P2RY6)、プリン作動性受容体P2Y(P2RY11)、プリン作動性受容体P2Y(P2RY12)、プリン作動性受容体P2Y(P2RY13)、プリン作動性受容体P2Y(P2RY14)、副甲状腺ホルモン1受容体(PTH1R)、副甲状腺ホルモン2受容体(PTH2R)、血小板活性化因子受容体(PTAFR)、プロキネチシン受容体1(PROKR1)、プロキネチネシン受容体2(PROKR2)、プロラクチン放出ホルモン受容体(PRLHR)、プロスタグランジンD2受容体(DP)(PTGDR)、プロスタグランジンD2受容体2(PTGDR2)、プロスタグランジンE受容体1(PTGER1)、プロスタグランジンE受容体2(PTGER2)、プロスタグランジンE受容体3(PTGER3)、プロスタグランジンE受容体4(PTGER4)、プロスタグランジンF受容体(PTGFR)、プロスタグランジンI2(プロスタサイクリン)受容体(IP)(PTGIR)、トロンボキサンA2受容体(TBXA2R)、凝固因子IIトロンビン受容体(F2R)、F2R様トリプシン受容体1(F2RL1)、凝固因子IIトロンビン受容体様2(F2RL2)、F2R様トロンビン/トリプシン受容体3(F2RL3)、ピログルタミル化RFアミドペプチド受容体(QRFPR)、リラキシン/インスリン様ファミリーペプチド受容体1(RXFP1)、リラキシン/インスリン様ファミリーペプチド受容体2(RXFP2)、リラキシン/インスリン様ファミリーペプチド受容体3(RXFP3)、リラキシン/インスリン様ファミリーペプチド受容体4(RXFP4)、ソマトスタチン受容体1(SSTR1)、ソマトスタチン受容体2(SSTR2)、ソマトスタチン受容体3(SSTR3)、ソマトスタチン受容体4(SSTR4)、ソマトスタチン受容体5(SSTR5)、コハク酸受容体1(SUCNR1)、タキキニン受容体1(TACR1)、タキキニン受容体2(TACR2)、タキキニン受容体3(TACR3)、味覚1受容体メンバー1(TAS1R1)、味覚1受容体メンバー2(TAS1R2)、味覚1受容体メンバー3(TAS1R3)、味覚2受容体メンバー1(TAS2R1)、味覚2受容体メンバー3(TAS2R3)、味覚2受容体メンバー4(TAS2R4)、味覚2受容体メンバー5(TAS2R5)、味覚2受容体メンバー7(TAS2R7)、味覚2受容体メンバー8(TAS2R8)、味覚2受容体メンバー9(TAS2R9)、味覚2受容体メンバー10(TAS2R10)、味覚2受容体メンバー13(TAS2R13)、味覚2受容体メンバー14(TAS2R14)、味覚2受容体メンバー16(TAS2R16)、味覚2受容体メンバー19(TAS2R19)、味覚2受容体メンバー20(TAS2R20)、味覚2受容体メンバー30(TAS2R30)、味覚2受容体メンバー31(TAS2R31)、味覚2受容体メンバー38(TAS2R38)、味覚2受容体メンバー39(TAS2R39)、味覚2受容体メンバー40(TAS2R40)、味覚2受容体メンバー41(TAS2R41)、味覚2受容体メンバー42(TAS2R42)、味覚2受容体メンバー43(TAS2R43)、味覚2受容体メンバー45(TAS2R45)、味覚2受容体メンバー46(TAS2R46)、味覚2受容体メンバー50(TAS2R50)、味覚2受容体メンバー60(TAS2R60)、甲状腺刺激ホルモン放出ホルモン受容体(TRHR)、微量アミン関連受容体1(TAAR1)、ウロテンシン2受容体(UTS2R)、アルギニンバソプレシン受容体1A(AVPR1A)、アルギニンバソプレシン受容体1B(AVPR1B)、アルギニンバソプレシン受容体2(AVPR2)、オキシトシン受容体(OXTR)、アデニル酸シクラーゼ活性化ポリペプチド1(脳下垂体)受容体I型(ADCYAP1R1)、血管作動性腸管ペプチド受容体1(VIPR1)、血管作動性腸管ペプチド受容体2(VIPR2)、その任意の誘導体、その任意のバリアント、およびその任意のフラグメントからなる群より選択されるGPCRを含む。
を有するSV40ウイルスラージT抗原のNLS;ヌクレオプラスミンからのNLS(例えば
を持つヌクレオプラスミン二パーツNLS);アミノ酸配列
を有するc-myc NLS;配列
を有するhRNPA1 M9 NLS;インポーチン-アルファからのIBBドメインの配列
;筋腫Tタンパク質の配列
;ヒトp53の配列
;マウスc-abl IVの配列
;インフルエンザウイルスNS1の配列
;肝炎ウイルスデルタ抗原の配列
;マウスMx1タンパク質の配列
;ヒトポリ(ADP-リボース)ポリメラーゼの配列
;およびステロイドホルモン受容体(ヒト)グルココルチコイドの配列
に由来するNLS配列が挙げられる。
を含む、ペネトラチンと呼ばれるキイロショウジョウバエ転写因子アンテナペディア(Antennapaedia)の第3アルファヘリックスに由来しうる。別の例として、浸透性ペプチドは、例えば天然tatタンパク質のアミノ酸49〜57を含みうるHIV-1 tat塩基性領域アミノ酸配列を含むことができる。他の浸透性ドメインとして、ポリ-アルギニンモチーフ、例えばHIV-1 revタンパク質のアミノ酸34〜56の領域、ノナアルギニン、オクタアルギニンなどが挙げられる。(例えば、トランスロケーションペプチドおよびペプトイドの教示に関して本明細書に特に組み入れられる、Futaki et al.(2003)Curr Protein Pept Sci. 2003 April; 4(2): 87-9および446;ならびにWender et al.(2000)Proc. Natl. Acad. Sci. U.S.A 2000 Nov. 21; 97(24):13003-8;米国特許出願公開第20030220334号、同第20030083256号、同第20030032593号、および同第20030022831号を参照されたい)。ノナアルギニン(R9)配列を使用することができる。(Wender et al. 2000; Uemura et al. 2002)。融合を行う部位は、ポリペプチドの生物学的活性、分泌または結合特徴が最適化されるように選択することができる。
遺伝子調整ドメインを含む工学的に操作されたキメラ抗原受容体を図17に提供する。工学的に操作された人工組換え受容体は、細胞外ドメイン(ECD)、膜貫通ドメイン(TM)、およびICD (細胞内ドメイン)を線形の順序で含む。ECDは特異的リガンド結合活性を有する。TMは細胞膜にまたがり、ICDはゲノム操作機能を保有する。TMおよびICDはペプチドリンカー配列により連結され、ペプチド配列はプロテアーゼにより認識されることができる。受容体は細胞上に発現され、そのリガンドに結合することができる1701。リガンド結合に際して、プロテアーゼにつながれた(融合された)アダプタータンパク質は、タンパク質-タンパク質相互作用、クラスタ形成またはスキャフォールド媒介相互作用を介して受容体に動員される。アダプター−プロテアーゼが工学的に操作されたキメラ抗原受容体と結び付いた後に、プロテアーゼは受容体から遺伝子調整ドメインを放出する1705。次いで、遺伝子調整ドメインは、核に自由に移動して、標的遺伝子を調節または編集する1709。ICDは転写因子を含むことができ、遺伝子発現またはエピジェネティクス(Nu, 核)を調整することができる。
本実施例は、工学的に操作された組換えキメラ受容体システムの3つのクラスについて記述する。これらの受容体にはGタンパク質共役受容体(GPCR)、インテグリン、およびNotchが含まれ、これらはがん微小環境に関連するさまざまなタイプのリガンドおよびシグナルを自然に検出する。例えば、7回膜貫通ドメイン受容体、7TM受容体、ヘプタヘリックス受容体、セルペンチン受容体、およびGタンパク質結合受容体(GPLR)として知られるGPCRは、細胞外の分子を感知し、シグナル伝達経路および、最終的には、細胞内部の細胞応答を活性化する受容体の大きなタンパク質ファミリーを構成する。
Gタンパク質共役受容体は真核生物においてのみ見出される。これらの受容体に結合し活性化するリガンドは非常に多様であり、光感受性化合物、臭気、フェロモン、ホルモン、および神経伝達物質を含む。GPCRリガンドは、小分子からペプチドまで大型タンパク質までサイズが異なる。注目すべきことに、Gタンパク質共役受容体は多くの疾患に関与しており、現代の全医薬品のおよそ40%の標的でもある。Gタンパク質共役受容体を伴う天然の主要なシグナル伝達経路は、cAMPシグナル経路、またはホスファチジルイノシトールシグナル経路のいずれかを伴う、複雑なものでありうる。
代替的な構成において、本開示の合成GPCRは切断モエティを含み、アダプターポリペプチドはdCas9-エフェクタードメインを含む。例えば、図21Bに示されるように、dCas9-VPR (VP64、p65AD、およびRtaを含む三要素アクチベータ融合物) 2161は、TEV切断可能配列2181を介して、β2-アレスチンのような、アダプタータンパク質2171に融合することができる。β2-アレスチン-dCas9-VPRは、β2-アレスチン-dCas9-VPRの核外移行を増強するために、2コピーの核外移行シグナル(NES)を含むこともできる。TEVプロテアーゼ2191は、この構成において、GPCR 2100 (GPCR-プロテアーゼ)に融合することができる。β2-アレスチン-dCas9-VPRが活性化GPCR-プロテアーゼに動員されると、プロテアーゼはTEV-切断可能配列を切断し、β2-アレスチン-dCas9-VPRポリペプチドからdCas9-VPRを放出しうる。
dCas9-エフェクタードメイン、例えば、dCas9-アクチベータドメインに融合された工学的に操作されたインテグリンも本明細書において提供される(図22A)。異なる対のαサブユニットおよびβサブユニットを含むインテグリンは、フィブロネクチン、コラーゲン、ラミニンなどのような多様なマトリックスシグナルを感知することができる。dCas9-VPR-mCherryは、TEV切断可能なペプチドリンカー配列を介して、任意のインテグリン、例えば、α5β1インテグリンのαサブユニットまたはβサブユニットのいずれかに融合された2201。TEVプロテアーゼは、リガンド結合によって対合インテグリンに条件的に動員されたタンパク質であるパキシリンに連結された2221。レポーター遺伝子に結合できるsgRNAを宿主細胞に導入した2231。さらに、転写レポーター遺伝子(H2B-GFP遺伝子)を導入して、sgRNAガイドdCas9-VPR制御活性化を視覚化した2241。受容体発現対照として、scFv、mCherryおよびVPRに連結されたインテグリンを用いた2211。実験において用いられた他の対照には、dCas9-10xGCN4対照が含まれる2251。図22Bに示されるように、リガンドなしの、βサブユニットに連結されたdCas9-アクチベータドメイン(図22D、「B」)は、最小のGFPシグナルをもたらした(GFPのゲノムコピーをレポーターシグナルとして用い核へのdCas9-VPRの「放出された」量を検出する)。フィブロネクチンの存在下において、高いGFP発現が検出され、キメラインテグリン-dCas9タンパク質がリガンド結合の際に転写を活性化することが示唆された。コラーゲンの存在下において、キメラインテグリン-dCas9タンパク質はレポーター遺伝子の転写を活性化しなかった。リガンド結合によるインテグリンの活性化に加えて、表面結合によるインテグリン活性化はまた、dCas-9VPRの放出およびGFP発現をもたらす。インテグリン-dCas9-VPR + パキシリン-プロテアーゼ + sgRNAシステムは、接着細胞において発現されると、浮遊培養物と比較して高いレベルの蛍光レポータータンパク質を生じる(図22C)。dCas9-VPRがαサブユニットに連結されている場合(図22D、「C」)、パキシリンはβ-インテグリン尾部に特異的に結合するので、インテグリンの活性化はβサブユニットに連結されたdCas9-VPR (図22E、「A+B」)と比較してGFPの最小発現をもたらす(図22E、「A+C」)。
dCas9-アクチベータドメインを含むキメラNotch受容体も提供される(図24A〜24D)。1つの態様において、NotchはTEVペプチド切断配列リンカーなしでdCas9-アクチベータに直接融合された。第2の態様において、NotchはTEVペプチド切断配列を介してdCas9-アクチベータに直接融合された。TEVプロテアーゼはNotchアダプタータンパク質であるプレセニリン-1 (PS-1)に連結された。プレセニリン1は、γセクレターゼを含めて、細胞内のいくつかのタンパク質の、調節されたタンパク質分解事象を媒介する、プレセニリン複合体中の4つのコアタンパク質の1つである。各キメラ受容体の発現コンストラクトを作製し、HEK293細胞のような、宿主細胞に導入した。Notch-dCas9-VPR-mCherryポリペプチドのアミノ酸配列の一例は、SEQ ID NO:5に提供されている。
本実施例は、細胞療法に対する新規のアプローチ、すなわち病的な微小環境を認識でき、正確な治療作用で応答できる改変された免疫細胞の作製について記述する。患者の免疫細胞は、特定の細胞および細胞の局所環境を感知し、それに応答しうる本来的に複雑なシステムを利用するので、これらの治療法のために有望な試薬である。
本実施例は、NotchおよびCRISPR/Casタンパク質を組み合わせて、標的細胞認識(Notchを介した)およびプログラム細胞応答(CRISPR/dCas9を介した)のためのカスタマイズ可能な直交シグナル伝達系を生成するキメラ受容体について記述する。接触媒介Notch-Deltaシグナル伝達およびRNAガイドCRISPRゲノム工学を利用する高度にプログラム可能ながん認識プラットフォームが本明細書において提供される。これらのキメラNotch受容体(図24A〜24C)は、NotchのNICDをCas9構成要素で置換することにより、任意の標的遺伝子を活性化するように用いることができる。Notch-Deltaの相互作用により、広範囲の複雑な細胞挙動を制御することができる。本明細書において記述されるキメラ抗原受容体は、局所細胞-細胞微小環境に応答してT細胞の転写および細胞活性を調整するために用いることができる。
Notch-Delta活性化の単純さにより、シグナル応答の同調が可能とされる。数学的モデリングおよび実験は、NotchとDeltaの間の相互cis阻害が内因性Notchと合成Notchの両方が存在する場合の応答機能にどのように影響するかを調べることができる。これは、さまざまな強度のプロモーターを用いて同じ細胞内でcaN-dCas9-EGFPおよびDelta-mCherryの両方を発現させることによって行うことができる。
本明細書において記述されるCD47結合キメラ抗原Notch受容体-dCas9融合タンパク質は、がんの進行および免疫回避のような、がんの分野において用いることができる。CD47結合caN-dCas9受容体が、がんにおける免疫回避を媒介または調節する有効性を試験するために、以前に記述されたCD47scFv-Notch-dCas9受容体をTHP-1由来マクロファージにおいて発現させることができる。ヒトCD47をCHO細胞において発現させることができる。SIRPα(内因性応答)、マクロファージ上のcaN-dCas9、および標的CHO細胞上のhCD47の表面発現のフローサイトメトリー分析を実施して、これらの細胞の理論モデルを反復様式で定式化および検証することができる。
キメラ人工GPCR受容体は、AVPR2 (27アミノ酸残基)に由来するC末β2-アレスチン結合部位を有する完全長GPCR、プロテアーゼ切断部位、および三要素エフェクタードメイン(VPR)を有するヌクレアーゼ-デッドCas9 (dCas)を含むように産生された(図28A)。キメラβ2-アレスチン-プロテアーゼは、リガンド媒介性GPCR活性化時にプロテアーゼ切断部位を認識かつ切断する。dCas9-VPRは、tetOプロモーターを特異的に標的とする単一ガイドRNA (sgTet, SEQ ID NO:2; gtacgttctctatcactgata)とともに核へ移動し、レポータールシフェラーゼ遺伝子の遺伝子発現につながる。dCas9-VPR、CXCR4、またはキメラCXCR4-dCas9-VPRをコードする以下の発現コンストラクトの1つを、tetO駆動ルシフェラーゼ遺伝子およびβ2-アレスチン-プロテアーゼコンストラクトを安定に発現するHEK293細胞にトランスフェクトした。トランスフェクトした細胞を、さまざまな濃度にて18時間CXCL12 (CXCR4のリガンド)で処理した。ルシフェラーゼ発現の程度を測定するために、ルシフェラーゼによって切断された場合に、発光シグナルが放出され検出可能であるように、ルシフェリンが導入された(図28B)。
キメラ人工インテグリン受容体は、完全長β1-インテグリン、プロテアーゼ切断部位、および三要素エフェクタードメイン(VPR)を有するヌクレアーゼ-デッドCas9 (dCas)を含むように産生することができる(図29A)。αβ-インテグリン二量体に結合する細胞外マトリックスは、表面上に固定化され、または別の細胞により提示されることができる。インテグリン活性化は、β-インテグリンのC末へのキメラパキシリン-プロテアーゼの結合、プロテアーゼ切断部位の切断、およびdCas9-VPRの核への移動をもたらす。パキシリンは、β-インテグリンのHDRKモチーフを認識する。dCas9および上流活性化配列(UAS)プロモーターを標的とする単一ガイドRNA, sgUAS (SEQ ID NO:1; gtactccgacctctagtgt)は、レポーター遺伝子、例えば蛍光シトリンタグ付きのヒストン2Bをコードする遺伝子の発現を活性化することができる。UAS駆動H2B-シトリン遺伝子およびパキシリン-プロテアーゼコンストラクトの両方を安定に発現するHEK293細胞に、キメラβ1-インテグリン-dCas9-VPRおよびα-インテグリンをコードする発現コンストラクトをトランスフェクトした。トランスフェクトした細胞をECM被覆表面上で培養した。フローサイトメトリーデータは、ECMによって接触されなかった細胞と比較して、ECM表面によって接触された細胞がH2B-シトリンを過剰発現したことを示す(図29B)。
リガンド結合時の第1受容体が第2受容体の発現を活性化して「AND」ゲートを形成するように、2つの受容体を一緒に連結することによるものである。このようにして、両方のリガンドの存在のみが細胞応答を誘発することができる。「A AND NOT B」ゲートも可能である。例えば、がん細胞は第1の抗原を有するが、しかし第2の異なる抗原を欠くかどうかを判定するために、受容体Aをアクチベータに融合させることができ、受容体Bをリプレッサに融合させることができる。これによって、さらに特異的なシグナル操作に向けて複数のがん関連シグナルの統合が可能になる。このシステムはまた、活性化の際に細胞のエピジェネティック状態を変化させることができる「遺伝記憶」の構築を試験するために用いることができる。
本明細書において開示されるヒトNOTCH1-Cas9キメラ受容体は、細胞外Deltaリガンドと結合すると、哺乳類遺伝子発現を工学的に操作するために膜結合Cas9を放出するように開発されている。これらのキメラ受容体は、強い、Delta依存性のCas9媒介レポーター遺伝子の発現および内因性遺伝子機能の調整を示す。このキメラ受容体-Cas9技術は、細胞外キュー(cue)依存性ゲノム工学を開拓し、これはシグナル伝達経路を精査し、微小環境-感知細胞機能を可能とするのに有用であることができる。
も融合キメラのC末へ導入し、バリアントNC4およびNC5を得た。NC4は1つの合成NLSを有するが、NC5はそうではない。NC5のみがH2BのDelta依存性活性化を示し(図31D)、適切な膜成熟が合成NLSによって損なわれ、NC5におけるようなMMSが適切な成熟を促進することを示唆していた。最後に、NC5およびsgUASはレポーター細胞へ安定に組み込まれ、Deltaの非存在下では最小の基本的H2B発現に基づいて単一のクローンが単離された。Deltaに応答して3倍のH2B活性化(図31Eおよび31F)が観察されたので、NC5デザインを下流研究に用いた。
は、化膿連鎖球菌Cas9の結晶構造においてヘリックス-リンカー-ヘリックスモチーフにマッピングされた。両ヘリックスの表面曝露は、インポーチン依存性核輸送のためのそれらのアクセス可能性を示唆していた(図35A)。dCas9-VPR-mCherryコンストラクトにおいてiNLSの6つのアルギニンまたはリジン残基をアラニン
に変異させるとHEK293レポーター細胞においてEGFP活性化が(18倍から4倍にまで)損なわれた。わずかな割合(およそ16%)の細胞がEGFPを活性化し、この変異iNLSバリアントが機能的なままであったこと、および/または他の非標準的な潜在NLSが未同定のままであることが示唆された(図35B)。dCas9-VPR-mCherryコンストラクトにおいてアルギニンおよびリジン残基をアラニン
に変異させることによってこのiNLSモチーフを破壊すると図35Cの代表的な共焦点顕微鏡画像において示されるように、ヒト胎児腎臓(HEK293T)細胞における核局在化およびEGFPレポーター活性化がひどく損なわれた。EGFPレポーターの代表的なヒストグラムが右側に示されている; 「ON」と考えられる細胞の割合は、トランスフェクトされていない「OFF」細胞を上回るレポーター強度を有していた。iNLS変異dCas9-VPRのN末に合成NLSを付加し戻すとEGFP活性化が部分的に回復し、dCas9のiNLSを変異させてもそのDNA結合機能は変化しないことが示唆された(図35D)。
遺伝子コンストラクトの作製
標準的な分子クローニング技法を実施して、本実施例において記述される全てのコンストラクトを組み立てた(表6および8)。全てのNotchキメラ受容体を、CMVプロモーターおよびジェネティシン耐性マーカー下でpcDNA3ベクターにクローニングした。全てのsgRNAコンストラクトを、U6プロモーターを有するかつピューロマイシン耐性マーカーまたは蛍光マーカーのいずれかを有するpHRベクターにクローニングした。
図31A〜31Fにおいて用いられた全ての細胞株は、細胞株T-Rex-CHO-K1 (Invitrogen)に基づいていた。UAS-H2B-シトリンおよび12xCSL-H2B-シトリンの安定な細胞クローンが得られた。製造業者の指示にしたがいレンチウイルス形質導入(全てのsgRNAおよびSV40-EGFPの)またはTransIT-LT1試薬(Mirus Bio)を用いたプラスミドトランスフェクションから、さらなる細胞株を作製し、引き続いて適切な抗生物質選択および維持を行った。2週間のピューロマイシンおよびジェネティシン選択の後、UAS-H2B-シトリン系統中のNC5およびsgUASを発現する安定にトランスフェクトされたクローンをFACSによって単離した。全てのCHO細胞株を加湿インキュベーター中、5% CO2で37℃にて、10% Tet System Approved FBS (Clontech)、100 U/mLのペニシリンおよびストレプトマイシン、2 mM L-グルタミン(Gibco)および10 μg/mLのブラストサイジン(VWR International)を補充したEarle’s Salts (Irvine Scientific)を有するAlpha MEM中で増殖させた。
レンチウイルスのパッケージングのためにHEK293T細胞(ATCC)を用いた。細胞を5% CO2で37℃にて、10% Tet System Approved FBS (Clontech)ならびに100 U/mLのペニシリンおよびストレプトマイシン(Gibco)を補充したGlutaMAX(商標)培地(Thermo Fisher)を含むDMEM高グルコース中で維持した。細胞を1日目に6ウェルプレート形式(Corning)において2.0〜3.0×105細胞/mLで播種した。2日目に、細胞はトランスフェクションの時点で50〜70%の集密度であった。各ウェルについて、pHRプラスミドベクター1.51 μg/mL、dR8.91 1.32 μgおよびpMD2.G (Addgene) 165 ngを、TransIT-LT1試薬7.5 μLを含むOpti-MEM還元血清培地(Gibco) 250 μL中で混合し、室温で15〜30分間インキュベートした。トランスフェクション複合体溶液を、HEK293T培養液に滴下して均等に分配した。3日目に培地を、下流の形質導入に適した新鮮な培地(例えば、CHO細胞株の場合にはAlpha MEM)と交換した。4日目に、レンチウイルスを無菌シリンジで上清から採取し、-80℃での保存または標的細胞培養物の即時形質導入のために0.45 μmのポリフッ化ビニリデンフィルタ(Millipore)を通してクライオバイアルにろ過した。
Deltaの表面吸着: 本実施例において記述される実験は、1.5×104細胞/mLにて24ウェルプレートまたは48ウェルプレート(Corning)上にプレーティングした細胞で行われた。8-ヒスチジンタグを有するDLL4の親和性増強バリアント(E12)を用いて、2.15 μg/mLの飽和濃度でDeltaをプレート表面に吸着させ、細胞播種の前に37℃で2時間インキュベートした。CHO細胞での実験のために、5 μg/mLのハムスターフィブロネクチン(Innovative Research)もDeltaと一緒に吸着させた。
細胞をトリプシン処理し、Scanford FACScan分析器(Becton Dickinson)および標準的なプロトコルを用いてレポーター蛍光またはタンパク質免疫蛍光について分析した。細胞内タンパク質の場合、細胞をトリプシン処理し、4%パラホルムアルデヒド溶液中で15分間固定し、PBS中2%の正常ロバ血清(Thermo Fisher)を含む0.3% Triton-X 100 (Sigma)の溶液中で適切な一次抗体とともに室温で2時間インキュベートした。CDKN1Bに対する一次抗体(D69C12, Cell Signaling)を、製造業者の提案にしたがった濃度で用いた。次いで、細胞サンプルを、適切な種特異的Alexa 647ロバ二次抗体(Life Technologies)と1000分の1希釈で30分間インキュベートした。二次抗体のみ染色した細胞を陰性対照として用いた。
場合によっては、インビボでの適用のために、最小のNC5受容体バリアントを開発することが望まれうる。1つの関心領域はNECDであり、これはおよそ1,700アミノ酸である(dCas9, およそ1,300アミノ酸と比較して)。NECDドメインは、複数の上皮成長因子(EGF)リピートからなり; 機能的分析によって上皮成長因子(EGF)リピート11および12が重要なDelta結合単位であることが正確に示された。EGF 11, 12リピートは系統発生の全体にわたって高度に保存されている。ヒト、アフリカツメガエル、ゼブラフィッシュ、およびショウジョウバエ相同体のEGF 11, 12リピートのアライメントは、高度に保存されたコンセンサス残基の存在を示す(図37A)。図37Bは、機能的に最小のNC5キメラ受容体バリアントを系統的に判定するように構築された一連の欠失バリアントおよび完全長NECDの模式図を提供する。対応する最小NC5受容体バリアント(ヒストグラム, 右)でトランスフェクトされ、Deltaとともに培養(特別の定めのない限り3日間)されたHEK293T細胞のEGFPレポーター強度ヒストグラムを提供する。全36個のEGFリピートの欠失は、Delta活性化の完全な喪失をもたらす(delta EGF, 欠損)。ショウジョウバエNotchにおいて、機能的最小バリアントは、EGF 11,12 (例えば、EGF(10-12], Rebay, I. et al. Cell 67, 687-699 (1991)にあるような区間表記)のみを保持することによって報告されている。しかしながら、ヒトNECDのEGF(10-12]バリアントは、野生型hNECDと比べて活性化の低下(13.5%, 図37B)を示した。これは、ヒトNotchの他のEGFリピートがNotch-Delta相互作用の安定性に寄与しうることを示唆していた。EGF11,12に隣接する1〜2個のEGFリピートの再導入は、EGF 11,12単独よりも悪くなり、活性化の完全な喪失をもたらした。対照的に、さらに3〜5個のEGFリピートを加えると、EGF(7-14]バリアントが最も高い活性化率(83.5%)を示し、活性化効率のより良好な回復が得られた。注目すべきことに、EGF(7-14]バリアントは、野生型NECDの長さのわずか3分の1である。
最小のNC5受容体バリアントでの2つの遺伝子の同時活性化は、HEK293T細胞における複数のsgRNA (1遺伝子につき2つ)−すなわちCXCR4を標的とし(sgCXCR4)かつCD95を標的とする(sgCD95)−によって、達成された。「遊離」dCas9-VPRおよびsgCXCR4またはsgCD95により、非標的指向sgRNA (例えば、sgNT)と比較して5.6倍または3.5倍の上方制御が観察された。CXCR4およびCD95の同時活性化は、それぞれsgNTに対して3.7倍および4.6倍の増加をもたらした(図38)。最小EGF(7-14] NC5受容体バリアントおよび両方のsgRNAを用い、dCas9-VPR+sgNTと比べて、Delta無しで、DAPTだけで、またはDeltaおよびDAPT有りで培養された細胞において、両遺伝子の有意な上方制御は観察されなかった。これらの細胞がDelta上で培養された場合、dCas9-VPR+sgNTを有する細胞と比較して、CXCR4 (2.2倍の上方制御)およびCD95 (1.7倍の上方制御)の同時活性化が観察された(図38)。
SEQ ID NO:1
sgUAS
SEQ ID NO:2
sgTET
SEQ ID NO:3
CXCR4-dCas9-VPR-mCherry [CXCR4-V2尾部-TEV切断部位-dCas9-VPR-NLS-mCherry-HAタグ-リンカー]
SEQ ID NO:4
CXCR4
SEQ ID NO:5
V2尾部
SEQ ID NO:6
TEV切断部位
SEQ ID NO:7
dCas9
SEQ ID NO:8
VPR (太字のNLS, 下線付きのリンカー)
SEQ ID NO:9
NLS
SEQ ID NO:9
mCherry
SEQ ID NO:10
HAタグ
SEQ ID NO:11
リンカー
SEQ ID NO:12
ITGB1-dCas9-VPR-mCherry [インテグリンβ1-TEV切断部位-dCas9-VPR-NLS-mCherry-HAタグ-リンカー]
SEQ ID NO:13
インテグリンβ1
SEQ ID NO:14
TEV切断部位
SEQ ID NO:15
dCas9
SEQ ID NO:16
VPR (太字のNLS、下線付きのリンカー)
SEQ ID NO:17
NLS
SEQ ID NO:18
mCherry
SEQ ID NO:19
HAタグ
SEQ ID NO:20
リンカー
SEQ ID NO:21
Notch-dCas9-VPR-mCherry [hNECD-TM-hNICD-dCas9-VPR-mCherry-HAタグ-リンカー]
SEQ ID NO:22
hNECD
SEQ ID NO:23
TM
SEQ ID NO:24
hNICD
SEQ ID NO:25
dCas9
SEQ ID NO:26
下線付きのリンカー配列を有するVPR
SEQ ID NO:27
mCherry
SEQ ID NO:28
HAタグ
SEQ ID NO:29
HAタグとVPRとの間のリンカー
Claims (114)
- 細胞内での標的ポリヌクレオチドの発現を調節するためのシステムであって、
(a) 抗原に結合する際に修飾されるキメラ受容体ポリペプチドであって、受容体修飾がコンフォメーション変化または化学修飾を含む、キメラ受容体ポリペプチド;
(b) 該受容体修飾に応答して該受容体に結合するキメラアダプターポリペプチド;
(c) 切断認識部位に連結されたアクチュエータモエティを含む遺伝子調整ポリペプチド(GMP)であって、該切断認識部位の切断の際に該アクチュエータモエティが活性化されて標的ポリヌクレオチドと複合体形成する、GMP; および
(d) 該切断認識部位に近接している場合に該切断認識部位を切断する、切断モエティ
を含み、
ここで:
(i) 該GMPが該キメラ受容体ポリペプチドの細胞内領域の一部分を形成し、かつ該切断モエティが該キメラアダプターポリペプチドの一部分を形成する;
(ii) 該GMPが該キメラアダプターポリペプチドの一部分を形成し、かつ該切断モエティが該キメラ受容体ポリペプチドの細胞内領域の一部分を形成する; または
(iii) 該切断モエティが、該受容体修飾に応答して該キメラ受容体ポリペプチドに結合する第2アダプターポリペプチドと複合体形成し、かつ該GMPが該キメラアダプターポリペプチドの一部分を形成する、
前記システム。 - 受容体がSEQ ID NO: 39を含まない、請求項1記載のシステム。
- 標的ポリヌクレオチドがゲノムDNAである、請求項1記載のシステム。
- 標的ポリヌクレオチドがRNAである、請求項1記載のシステム。
- 修飾がリン酸化である、請求項1記載のシステム。
- アクチュエータモエティがCasタンパク質であり、かつ前記システムが、Casタンパク質と複合体を形成するために活性なガイドRNAをさらに含む、請求項1記載のシステム。
- (i) アクチュエータモエティが、ガイドRNAと複合体形成していてもよいRNA結合タンパク質(RBP)であり、かつ (ii) 前記システムが、該ガイドRNAと複合体を形成することができるCasタンパク質をさらに含む、請求項1記載のシステム。
- Casタンパク質がDNA切断活性を実質的に欠く、請求項6または7記載のシステム。
- (i) GMPがキメラアダプターポリペプチドの一部分を形成し、(ii) 切断認識部位の切断が、キメラアダプターポリペプチドを受容体から放出するのに有効であり、かつ (iii) 前記システムが、修飾された受容体に結合するGMPを含むさらなるキメラアダプターポリペプチドを含む、請求項1記載のシステム。
- 受容体修飾が複数の修飾部位での修飾を含み、各修飾部位が、アダプターポリペプチドに結合するのに有効である、請求項1記載のシステム。
- 切断認識部位がポリペプチド配列を含み、かつ切断モエティがプロテアーゼ活性を含む、請求項1記載のシステム。
- 切断認識部位がジスルフィド結合を含み、かつ切断モエティが酸化還元酵素活性を含む、請求項1記載のシステム。
- 切断認識部位が、インテイン配列の第2部分と反応してアクチュエータモエティを放出する、該インテイン配列の第1部分を含む、請求項1記載のシステム。
- 受容体が膜貫通受容体である、請求項1記載のシステム。
- 受容体が核内受容体である、請求項1記載のシステム。
- アクチュエータモエティが、標的ポリヌクレオチドの物理的妨害によって、または標的ポリヌクレオチドの発現を抑制もしくは増強するのに有効なさらなる因子の動員によって、標的ポリヌクレオチドの発現を調節する、請求項1記載のシステム。
- アクチュエータモエティが、標的ポリヌクレオチドの発現を増加させるのに有効なアクチベータを含む、請求項1記載のシステム。
- アクチュエータモエティが、少なくとも1つの核局在化シグナル(NLS)に連結される、請求項1記載のシステム。
- キメラ受容体ポリペプチドが、細胞の特定の領域へ受容体を輸送させる少なくとも1つの標的指向配列に連結される、請求項1記載のシステム。
- 標的指向配列が、核、細胞質、ミトコンドリア、小胞体(ER)、クロロプラスト、アポプラスト、ペルオキシソームまたは形質膜へ受容体を輸送させる、請求項19記載のシステム。
- 標的指向配列が、核外移行シグナル(NES)を含む、請求項19記載のシステム。
- 標的指向配列が、形質膜を標的とするペプチドを含む、請求項19記載のシステム。
- キメラアダプターポリペプチドが、細胞の特定の領域へアダプターを輸送させる少なくとも1つの標的指向配列に連結される、請求項1記載のシステム。
- 標的指向配列が、核、細胞質、ミトコンドリア、小胞体(ER)、クロロプラスト、アポプラスト、ペルオキシソームまたは形質膜へキメラアダプターポリペプチドを輸送させる、請求項23記載のシステム。
- 標的指向配列が、核外移行シグナル(NES)を含む、請求項23記載のシステム。
- 標的指向配列が、形質膜を標的とするペプチドを含む、請求項23記載のシステム。
- 受容体がポリペプチド折畳みドメインに連結される、請求項1記載のシステム。
- キメラアダプターポリペプチドが、ポリペプチド折畳みドメインに連結される、請求項1記載のシステム。
- 細胞内での標的ポリヌクレオチドの発現を調節する方法であって、
(a) キメラ受容体ポリペプチドを抗原に曝露する段階であって、ここで (i) 抗原への曝露の際に受容体が修飾され、かつ (ii) 受容体修飾がコンフォメーション変化または化学修飾を含む、段階;
(b) 該受容体修飾に応答してキメラアダプターポリペプチドを該キメラ受容体ポリペプチドに結合させて、遺伝子調整ポリペプチド(GMP)と切断モエティとの間で複合体を形成させる段階であって、ここで該GMPは切断認識部位に連結されたアクチュエータモエティを含む、段階; および
(c) 該切断認識部位を該切断モエティによって切断する段階であって、ここで該切断認識部位の切断の際に該アクチュエータモエティが活性化されて標的ポリヌクレオチドと複合体形成し、それにより細胞内での標的ポリヌクレオチドの発現を調節する、段階
を含み;
ここで:
(i) 該GMPが該キメラ受容体ポリペプチドの細胞内領域の一部分を形成し、かつ該切断モエティが該キメラアダプターポリペプチドの一部分を形成する;
(ii) 該切断モエティが該キメラアダプターポリペプチドの一部分を形成し、かつ該GMPが該キメラ受容体の細胞内領域の一部分を形成する; または
(iii) 該切断モエティが、該受容体修飾に応答して該受容体に結合する第2アダプターポリペプチドと複合体形成し、かつ該GMPが該キメラアダプターポリペプチドの一部分を形成する、
前記方法。 - 受容体がSEQ ID NO: 39を含まない、請求項29記載の方法。
- 標的ポリヌクレオチドがゲノムDNAである、請求項29記載の方法。
- 標的ポリヌクレオチドがRNAである、請求項29記載の方法。
- 修飾がリン酸化である、請求項29記載の方法。
- アクチュエータモエティが、ガイドRNAと複合体を形成するCasタンパク質である、請求項29記載の方法。
- アクチュエータモエティが、Casタンパク質と複合体を形成するガイドRNAと複合体形成したRNA結合タンパク質(RBP)である、請求項29記載の方法。
- Casタンパク質がDNA切断活性を実質的に欠く、請求項34または35記載の方法。
- (i) GMPがキメラアダプターポリペプチドの一部分を形成し、(ii) 該キメラアダプターポリペプチドが、切断認識部位の切断後に受容体から放出され、かつ (iii) GMPを含むさらなるキメラアダプターポリペプチドが、修飾された受容体に結合する、請求項29記載の方法。
- 受容体修飾が複数の修飾部位での修飾を含み、各修飾部位が、キメラアダプターポリペプチドに結合するのに有効である、請求項29記載の方法。
- 切断認識部位がポリペプチド配列を含み、かつ切断モエティがプロテアーゼ活性を含む、請求項29記載の方法。
- 切断認識部位がジスルフィド結合を含み、かつ切断モエティが酸化還元酵素活性を含む、請求項29記載の方法。
- 切断認識部位が、インテイン配列の第2部分と反応してアクチュエータモエティを放出する、該インテイン配列の第1部分を含む、請求項29記載の方法。
- 受容体が膜貫通受容体である、請求項29記載の方法。
- 受容体が核内受容体である、請求項29記載の方法。
- アクチュエータモエティが、標的ポリヌクレオチドの物理的妨害によって、または標的ポリヌクレオチドの発現を抑制もしくは増強するのに有効なさらなる因子の動員によって、標的ポリヌクレオチドの発現を調節する、請求項29記載の方法。
- アクチュエータモエティが、標的ポリヌクレオチドの発現を増加させるのに有効なアクチベータを含む、請求項29記載の方法。
- キメラ細胞内受容体であって、
(a) 抗原に特異的に結合する抗原相互作用ドメイン; および
(b) 抗原相互作用ドメインに連結されたアクチュエータモエティ
を含み、
ここで:
(i) キメラ細胞内受容体が抗原結合に応答して修飾され;
(ii) キメラ受容体ポリペプチドが、修飾に応答して細胞の核に移動し; かつ
(iii) アクチュエータモエティが、核内の標的ポリヌクレオチドと複合体形成する、
前記受容体。 - アクチュエータモエティが、ガイドRNAと複合体を形成するCasタンパク質である、請求項46記載のシステム。
- Casタンパク質がDNA切断活性を実質的に欠く、請求項47記載のキメラ細胞内受容体。
- アクチュエータモエティが、標的ポリヌクレオチドの物理的妨害によって、または標的ポリヌクレオチドの発現を抑制もしくは増強するのに有効なさらなる因子の動員によって、標的ポリヌクレオチドの発現を調節する、請求項46記載のキメラ細胞内受容体。
- アクチュエータモエティが、標的ポリヌクレオチドの発現を増加させるのに有効なアクチベータを含む、請求項46記載のキメラ細胞内受容体。
- 抗原がホルモンである、請求項46記載のキメラ細胞内受容体。
- アクチュエータモエティが、少なくとも1つの核局在化シグナル(NLS)に連結される、請求項46記載のキメラ細胞内受容体。
- 細胞の特定の領域へ受容体を輸送させる少なくとも1つの標的指向配列に連結される、請求項46記載のキメラ細胞内受容体。
- 標的指向配列が、核、細胞質、ミトコンドリア、小胞体(ER)、クロロプラスト、アポプラスト、またはペルオキシソームへ受容体を輸送させる、請求項53記載のキメラ細胞内受容体。
- 標的指向配列が、核外移行シグナル(NES)を含む、請求項53記載のキメラ細胞内受容体。
- 標的指向配列が、形質膜を標的とするペプチドを含む、請求項53記載のキメラ細胞内受容体。
- 受容体がポリペプチド折畳みドメインに連結される、請求項46記載のキメラ細胞内受容体。
- 核を含む細胞内での標的ポリヌクレオチドの発現を調節する方法であって、
(a) キメラ細胞内受容体を抗原に曝露する段階であって、ここで (i) 該受容体が抗原相互作用ドメインおよびアクチュエータモエティを含み、かつ (ii) 該抗原への曝露の際に該受容体が修飾される、段階;
(b) 該修飾された受容体を核に移動させる段階; ならびに
(c) アクチュエータモエティと標的ポリヌクレオチドとの間で複合体を形成する段階
を含む、前記方法。 - アクチュエータモエティが、ガイドRNAと複合体を形成するCasタンパク質である、請求項58記載の方法。
- Casタンパク質がDNA切断活性を実質的に欠く、請求項58記載の方法。
- アクチュエータモエティが、標的ポリヌクレオチドの物理的妨害によって、または標的ポリヌクレオチドの発現を抑制もしくは増強するのに有効なさらなる因子の動員によって、標的ポリヌクレオチドの発現を調節する、請求項58記載の方法。
- アクチュエータモエティが、標的ポリヌクレオチドの発現を増加させるのに有効なアクチベータを含む、請求項58記載の方法。
- 抗原がホルモンである、請求項58記載の方法。
- (a) 抗原相互作用ドメイン; および
(b) 切断認識部位に連結されたアクチュエータモエティを含む遺伝子調整ポリペプチド(GMP)
を含み、
ここで:
(i) キメラ受容体ポリペプチドが抗原結合に応答して修飾され;
(ii) 切断認識部位が、キメラ受容体ポリペプチドの修飾に応答して切断モエティにより切断され;
(iii) アクチュエータモエティが切断認識部位でキメラ受容体ポリペプチドから切断された後に、標的ポリヌクレオチドと複合体形成し; かつ
(iv) キメラ受容体ポリペプチドが、SEQ ID NO: 39を含まない、
キメラ受容体ポリペプチド。 - 切断認識部位が、抗原相互作用ドメインとアクチュエータモエティとに挟まれている、請求項64記載のキメラ受容体ポリペプチド。
- 抗原相互作用ドメインが、キメラ受容体ポリペプチドの細胞外領域の一部分を形成し、かつGMPが、該キメラ受容体ポリペプチドの細胞内領域の一部分を形成する、請求項64記載のキメラ受容体ポリペプチド。
- アクチュエータモエティが、切断認識配列の切断後に細胞核に移動する、請求項64記載のキメラ受容体ポリペプチド。
- 抗原結合に応答して細胞核に移動する核内受容体である、請求項64記載のキメラ受容体ポリペプチド。
- アクチュエータモエティが、ガイドRNAと複合体を形成するCasタンパク質である、請求項64記載のキメラ受容体ポリペプチド。
- アクチュエータモエティが、Casタンパク質と複合体を形成することができるガイドRNAと複合体形成していてもよいRNA結合タンパク質(RBP)である、請求項64記載のキメラ受容体ポリペプチド。
- Casタンパク質がDNA切断活性を実質的に欠く、請求項69または70記載のキメラ受容体ポリペプチド。
- 切断認識部位が、プロテアーゼの認識配列であるポリペプチド配列を含む、請求項64記載のキメラ受容体ポリペプチド。
- 切断認識部位が、インテイン配列の第2部分と反応してアクチュエータモエティを放出する、該インテイン配列の第1部分を含む、請求項64記載のキメラ受容体ポリペプチド。
- 切断認識部位がジスルフィド結合を含む、請求項64記載のキメラ受容体ポリペプチド。
- 膜貫通受容体である、請求項64記載のキメラ受容体ポリペプチド。
- 核内受容体である、請求項64記載のキメラ受容体ポリペプチド。
- アクチュエータモエティが、標的ポリヌクレオチドの物理的妨害によって、または標的ポリヌクレオチドの発現を抑制もしくは増強するのに有効なさらなる因子の動員によって、標的ポリヌクレオチドの発現を調節する、請求項64記載のキメラ受容体ポリペプチド。
- アクチュエータモエティが、標的ポリヌクレオチドの発現を増加させるのに有効なアクチベータを含む、請求項64記載のキメラ受容体ポリペプチド。
- アクチュエータモエティが、少なくとも1つの核局在化シグナル(NLS)に連結される、請求項64記載のキメラ受容体ポリペプチド。
- 細胞の特定の領域へ受容体を輸送させる少なくとも1つの標的指向配列に連結される、請求項64記載のキメラ受容体ポリペプチド。
- 標的指向配列が、核、細胞質、ミトコンドリア、小胞体(ER)、クロロプラスト、アポプラスト、ペルオキシソームまたは形質膜へ受容体を輸送させる、請求項80記載のキメラ受容体ポリペプチド。
- 標的指向配列が、核外移行シグナル(NES)を含む、請求項80記載のキメラ受容体ポリペプチド。
- 標的指向配列が、形質膜を標的とするペプチドを含む、請求項80記載のキメラ受容体ポリペプチド。
- ポリペプチド折畳みドメインに連結される、請求項64記載のキメラ受容体ポリペプチド。
- (a) 抗原に結合する際に修飾を受けた受容体に結合する受容体結合モエティ; および
(b) 該受容体結合モエティに連結された遺伝子調整ポリペプチド(GMP)であり、切断認識部位に連結されたアクチュエータモエティを含む、GMP
を含み、
ここで:
(i) 該切断認識部位が、受容体結合に応答して切断モエティにより切断可能であり; かつ
(ii) 該アクチュエータモエティが、該切断認識部位の切断に応答して標的ポリヌクレオチドと複合体形成するように作動可能である、
キメラアダプターポリペプチド。 - アクチュエータモエティが、切断認識配列の切断後に細胞核に移動するように作動可能である、請求項85記載のキメラアダプターポリペプチド。
- アクチュエータモエティが、ガイドRNAと複合体を形成するCasタンパク質である、請求項85記載のキメラアダプターポリペプチド。
- アクチュエータモエティが、Casタンパク質と複合体を形成することができるガイドRNAと複合体形成していてもよいRNA結合タンパク質(RBP)である、請求項85記載のキメラアダプターポリペプチド。
- Casタンパク質がDNA切断活性を実質的に欠く、請求項87または88記載のキメラアダプターポリペプチド。
- 切断認識部位が、プロテアーゼの認識配列であるポリペプチド配列を含む、請求項85記載のキメラアダプターポリペプチド。
- 切断認識部位が、インテイン配列の第2部分と反応してアクチュエータモエティを放出する、該インテイン配列の第1部分を含む、請求項85記載のキメラアダプターポリペプチド。
- 切断認識部位がジスルフィド結合を含む、請求項85記載のキメラアダプターポリペプチド。
- アクチュエータモエティが、標的ポリヌクレオチドの物理的妨害によって、または標的ポリヌクレオチドの発現を抑制もしくは増強するのに有効なさらなる因子の動員によって、標的ポリヌクレオチドの発現を調節する、請求項85記載のキメラアダプターポリペプチド。
- アクチュエータモエティが、標的ポリヌクレオチドの発現を増加させるのに有効なアクチベータを含む、請求項85記載のキメラアダプターポリペプチド。
- アクチュエータモエティが、少なくとも1つの核局在化シグナル(NLS)に連結される、請求項85記載のキメラアダプターポリペプチド。
- アダプターポリペプチドが、細胞の特定の領域へアダプターを輸送させる少なくとも1つの標的指向配列に連結される、請求項85記載のキメラアダプターポリペプチド。
- 標的指向配列が、核、細胞質、ミトコンドリア、小胞体(ER)、クロロプラスト、アポプラスト、ペルオキシソームまたは形質膜へアダプターを輸送させる、請求項96記載のキメラアダプターポリペプチド。
- 標的指向配列が、核外移行シグナル(NES)を含む、請求項96記載のキメラアダプターポリペプチド。
- 標的指向配列が、形質膜を標的とするペプチドを含む、請求項96記載のキメラアダプターポリペプチド。
- 細胞内での標的ポリヌクレオチドの発現を調節するためのシステムであって、
(a) 抗原に結合する際に修飾されるキメラ受容体ポリペプチドであって、受容体修飾がコンフォメーション変化または化学修飾を含む、キメラ受容体ポリペプチド;
(b) 該受容体修飾に応答して該受容体に結合するキメラアダプターポリペプチド;
(c) ペプチド切断ドメインに連結されたアクチュエータモエティであって、該ペプチド切断ドメインの切断の際にアクチュエータモエティが活性化されて該標的ポリヌクレオチドと複合体形成する、アクチュエータモエティ; および
(d) 該ペプチド切断ドメインに近接している場合に該ペプチド切断ドメインを切断する切断モエティ
を含み、
ここで:
(i) 該切断モエティが該受容体の細胞内部分を形成し、かつ該ペプチド切断ドメインに連結された該アクチュエータモエティが該キメラアダプターポリペプチドの一部分を形成する;
(ii) 該切断モエティが、該受容体修飾に応答して該受容体に結合する第2アダプターポリペプチドと複合体形成し、かつ該ペプチド切断ドメインに連結された該アクチュエータモエティが該キメラアダプターポリペプチドの一部分を形成する; または
(iii) 該切断モエティが該アダプターポリペプチドの一部分を形成し、かつ該ペプチド切断ドメインに連結された該アクチュエータモエティが該受容体の細胞内部分を形成する、
前記システム。 - 細胞内での標的ポリヌクレオチドの発現を調節するためのシステムであって、
(a) 抗原に結合する際に修飾されるキメラ受容体ポリペプチド受容体であって、受容体修飾がコンフォメーション変化または化学修飾を含む、キメラ受容体ポリペプチド;
(b) 該受容体修飾に応答して該受容体に結合するキメラアダプターポリペプチド;
(c) ペプチド切断ドメインに連結されたアクチュエータモエティであって、該ペプチド切断ドメインの切断の際にアクチュエータモエティが活性化されて該標的ポリヌクレオチドと複合体形成する、アクチュエータモエティ; および
(d) 該ペプチド切断ドメインに近接している場合に該ペプチド切断ドメインを切断する組換えプロテアーゼドメイン
を含み、
ここで:
(i) 該組換えプロテアーゼドメインが該受容体の細胞内部分を形成し、かつ該ペプチド切断ドメインに連結された該アクチュエータモエティが該キメラアダプターポリペプチドの一部分を形成する;
(ii) 該組換えプロテアーゼドメインが、該受容体修飾に応答して該受容体に結合する第2アダプターポリペプチドと複合体形成し、かつ該ペプチド切断ドメインに連結された該アクチュエータモエティが該キメラアダプターポリペプチドの一部分を形成し; または
(iii) 該組換えプロテアーゼドメインが該キメラアダプターポリペプチドの一部分を形成し、かつ該ペプチド切断ドメインに連結された該アクチュエータモエティが該受容体の細胞内部分を形成する、
前記システム。 - (a) 抗原に結合する細胞外抗原相互作用ドメイン;
(b) 膜貫通ドメイン; および
(c) Casタンパク質を含む細胞内遺伝子調整ドメイン
を含み、
ここで、ペプチド切断ドメインが該遺伝子調整ドメインのアミノ末端に位置し;
ここで、該抗原に該細胞外抗原相互作用ドメインが結合する際に、該遺伝子調整ドメインが、該ペプチド切断ドメインの切断によってキメラ受容体ポリペプチドから放出される、
前記キメラ受容体ポリペプチド。 - 抗原に結合する際に受容体修飾を受ける、請求項102記載のキメラ受容体ポリペプチド。
- 膜貫通ドメインがNotch受容体タンパク質の一部分、またはその任意の誘導体、バリアントもしくはフラグメントを含む、請求項102記載のキメラ受容体ポリペプチド。
- 膜貫通ドメインが、SEQ ID NO: 39またはそのフラグメントに対して少なくとも80%の同一性を有するアミノ酸配列を含む、請求項104記載のキメラ受容体ポリペプチド。
- Casタンパク質がDNA切断活性を実質的に欠く、請求項102記載のキメラ受容体ポリペプチド。
- Casタンパク質がCas9タンパク質である、請求項102記載のキメラ受容体ポリペプチド。
- 遺伝子調整ドメインが、標的ポリヌクレオチドの発現を増加させるのに有効なアクチベータドメインをさらに含む、請求項102記載のキメラ受容体ポリペプチド。
- 遺伝子調整ドメインが、標的ポリヌクレオチドの発現を減少させるのに有効なリプレッサドメインをさらに含む、請求項102記載のキメラ受容体ポリペプチド。
- 遺伝子調整ドメインが、該遺伝子調整ドメインが受容体から放出された後に細胞の特定の領域へ該遺伝子調整ドメインを輸送させる少なくとも1つの標的指向配列をさらに含む、請求項102記載のキメラ受容体ポリペプチド。
- 少なくとも1つの標的指向配列が、核局在化配列(NLS)を含む、請求項110記載のキメラ受容体ポリペプチド。
- 細胞の特定の領域へ受容体を輸送させる少なくとも1つの標的指向配列に連結される、請求項102記載のキメラ受容体ポリペプチド。
- ポリペプチド折畳みドメインに連結される、請求項102記載のキメラ受容体ポリペプチド。
- ペプチド切断ドメインが、プロテアーゼの認識配列を含む、請求項102記載のキメラ受容体ポリペプチド。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019504835A (ja) * | 2016-01-11 | 2019-02-21 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | キメラタンパク質および免疫治療の方法 |
WO2020179844A1 (ja) * | 2019-03-04 | 2020-09-10 | 公益財団法人東京都医学総合研究所 | Trk断片をコードする核酸構築物、及びその利用 |
Families Citing this family (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2841572B1 (en) | 2012-04-27 | 2019-06-19 | Duke University | Genetic correction of mutated genes |
GB201415347D0 (en) * | 2014-08-29 | 2014-10-15 | Ucl Business Plc | Signalling system |
EP3322800A4 (en) | 2015-07-13 | 2019-05-01 | University of Utah Research Foundation | PROCESS FOR THE PRODUCTION OF RED BLOOD BODIES AND BLOOD PLATES IN VITRO AND USES THEREOF |
US11970710B2 (en) | 2015-10-13 | 2024-04-30 | Duke University | Genome engineering with Type I CRISPR systems in eukaryotic cells |
MY196175A (en) | 2016-01-11 | 2023-03-20 | Univ Leland Stanford Junior | Chimeric Proteins And Methods Of Regulating Gene Expression |
US11649288B2 (en) | 2017-02-07 | 2023-05-16 | Seattle Children's Hospital | Phospholipid ether (PLE) CAR T cell tumor targeting (CTCT) agents |
WO2018160622A1 (en) | 2017-02-28 | 2018-09-07 | Endocyte, Inc. | Compositions and methods for car t cell therapy |
WO2018169983A1 (en) * | 2017-03-13 | 2018-09-20 | President And Fellows Of Harvard College | Methods of modulating expression of target nucleic acid sequences in a cell |
KR20190142775A (ko) | 2017-04-19 | 2019-12-27 | 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 | 조작된 항원 수용체를 발현하는 면역 세포 |
AU2018283155A1 (en) | 2017-06-14 | 2019-12-19 | Wisconsin Alumni Research Foundation | Modified guide RNAs, CRISPR-ribonucleotprotein complexes and methods of use |
US11325957B2 (en) | 2017-06-19 | 2022-05-10 | Cell Design Labs, Inc. | Methods and compositions for reducing the immunogenicity of chimeric notch receptors |
IL271883B1 (en) * | 2017-07-12 | 2024-04-01 | Refuge Biotechnologies Inc | Systems and methods for conditional regulation of gene expression |
US11584955B2 (en) * | 2017-07-14 | 2023-02-21 | Shanghai Tolo Biotechnology Company Limited | Application of Cas protein, method for detecting target nucleic acid molecule and kit |
GB201711470D0 (en) * | 2017-07-17 | 2017-08-30 | Univ Oxford Innovation Ltd | Chimeric receptors |
EP3703716A4 (en) * | 2017-11-02 | 2021-12-01 | California Institute of Technology | EXPRESSION OF NEUROPEPTIDES |
US11458129B2 (en) | 2017-11-02 | 2022-10-04 | California Institute Of Technology | Neurokinin antagonists and uses thereof |
US20200331985A1 (en) * | 2017-11-16 | 2020-10-22 | The Regents Of The University Of California | Force sensor cleavage domain containing chimeric polypeptides and methods of use thereof |
WO2019144061A1 (en) * | 2018-01-19 | 2019-07-25 | Duke University | Genome engineering with crispr-cas systems in eukaryotes |
WO2019141270A1 (zh) * | 2018-01-19 | 2019-07-25 | 科济生物医药(上海)有限公司 | SynNotch受体调控表达IL12 |
US11311576B2 (en) | 2018-01-22 | 2022-04-26 | Seattle Children's Hospital | Methods of use for CAR T cells |
EP3755712A1 (en) * | 2018-02-21 | 2020-12-30 | Cell Design Labs, Inc. | Chimeric transmembrane receptors and uses thereof |
CN112512594A (zh) * | 2018-03-23 | 2021-03-16 | 瑞非生物科技有限公司 | 经由基因调节多肽的条件性核定位的基因调节 |
WO2019199165A1 (en) * | 2018-04-10 | 2019-10-17 | Stichting Sanquin Bloedvoorziening | Chimeric notch receptors |
US10227576B1 (en) | 2018-06-13 | 2019-03-12 | Caribou Biosciences, Inc. | Engineered cascade components and cascade complexes |
WO2020072764A1 (en) * | 2018-10-03 | 2020-04-09 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Covalent adaptor synnotch and chimeric antigen receptors (cars) for programmable antigen-targeting |
WO2020072471A1 (en) * | 2018-10-05 | 2020-04-09 | University Of Utah Research Foundation | Methods of making platelets comprising modified receptors and uses thereof |
US11739320B2 (en) | 2018-11-05 | 2023-08-29 | Wisconsin Alumni Research Foundation | Gene correction of Pompe disease and other autosomal recessive disorders via RNA-guided nucleases |
EP3927830A4 (en) * | 2019-02-22 | 2022-11-30 | Refuge Biotechnologies, Inc. | CHIMERA POLYPEPTIDES AND METHODS OF USING THE SAME |
US20220204955A1 (en) * | 2019-04-26 | 2022-06-30 | Toolgen Incorporated | Target-specific crispr mutant |
WO2020227307A1 (en) * | 2019-05-07 | 2020-11-12 | Refuge Biotechnologies, Inc. | Systems and methods for nuclear localization of gene modulating polypeptides |
MA56037A (fr) * | 2019-05-28 | 2022-04-06 | Octant Inc | Système de relais de transcription |
CN110438161A (zh) * | 2019-08-08 | 2019-11-12 | 深圳市第三人民医院 | 利用Cas12a蛋白筛选双等位基因突变细胞株的方法 |
CN110812532A (zh) * | 2019-08-20 | 2020-02-21 | 中山大学 | 一种靶向促进皮质脊髓束连接以修复脊髓损伤的组织工程支架的构建方法 |
CN110607357B (zh) * | 2019-11-07 | 2023-09-19 | 益善生物技术股份有限公司 | 人pcdh10基因甲基化检测试剂盒 |
CN110938656B (zh) * | 2019-12-24 | 2021-12-28 | 中国大熊猫保护研究中心 | 重组表达大熊猫促卵泡生成素的载体、表达系统及制备方法 |
CN115552014A (zh) * | 2020-03-05 | 2022-12-30 | 瑞非生物科技有限公司 | 嵌合衔接子蛋白和调控基因表达的方法 |
CN111455046A (zh) * | 2020-03-13 | 2020-07-28 | 深圳市罗湖区人民医院 | 一种adgrg6增强子突变的核酸检测方法及其试剂盒 |
WO2021231773A1 (en) * | 2020-05-13 | 2021-11-18 | Good Therapeutics, Inc. | Compositions of protein complexes and methods of use thereof |
CN113735961B (zh) * | 2020-05-28 | 2024-02-20 | 厦门大学 | 一类雌激素相关受体β突变体及其应用 |
CA3190324A1 (en) * | 2020-07-29 | 2022-02-03 | The Board Of Trustees Of The Leland Stanford Junior University | Synthetic oligomerization systems for cell engineering and therapy |
CN114075272B (zh) * | 2020-08-10 | 2023-09-22 | 杭州俊丰生物工程有限公司 | 一种人神经调节蛋白4的制备方法 |
US11508453B2 (en) * | 2020-08-18 | 2022-11-22 | Micron Technology, Inc. | Encoding test data of microelectronic devices, and related methods, devices, and systems |
US20230302135A1 (en) * | 2020-08-26 | 2023-09-28 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Hybrid allosteric receptor-engineered stem cells |
CN112442107B (zh) * | 2020-11-18 | 2023-05-09 | 渤海大学 | 一种苦味抑制肽及其应用 |
CN112322739B (zh) * | 2020-11-24 | 2023-08-15 | 深圳市罗湖区人民医院 | 一种检测adgrg6高频突变位点的方法及试剂盒 |
US11661459B2 (en) | 2020-12-03 | 2023-05-30 | Century Therapeutics, Inc. | Artificial cell death polypeptide for chimeric antigen receptor and uses thereof |
US11883432B2 (en) | 2020-12-18 | 2024-01-30 | Century Therapeutics, Inc. | Chimeric antigen receptor system with adaptable receptor specificity |
CN117321202A (zh) * | 2021-02-19 | 2023-12-29 | 武汉大学 | 具有宽松pam要求的双链dna的编辑 |
CN113030048A (zh) * | 2021-03-09 | 2021-06-25 | 南京市产品质量监督检验院 | 一种基于fpr1通道功能的化学品致癌性体外检测方法 |
CN117597140A (zh) * | 2021-03-24 | 2024-02-23 | 加利福尼亚大学董事会 | 具有多种转录调控因子的杂合受体 |
CA3214171A1 (en) * | 2021-04-01 | 2022-10-06 | Triantafyllos P. Tafas | Systems and compositions for detecting a biological sample and methods thereof |
CN113999873B (zh) * | 2021-12-31 | 2022-05-20 | 北京市疾病预防控制中心 | 一种基因修饰的非人动物的构建方法及其应用 |
CN114686456B (zh) * | 2022-05-10 | 2023-02-17 | 中山大学 | 基于双分子脱氨酶互补的碱基编辑系统及其应用 |
WO2023220012A1 (en) * | 2022-05-11 | 2023-11-16 | Mayo Foundation For Medical Education And Research | Treating cancer |
CN116004697B (zh) * | 2022-06-30 | 2024-02-13 | 深圳技术大学 | 一种异源产虫草素的米曲霉工程菌及其构建方法与应用 |
CN116716349B (zh) * | 2023-08-01 | 2023-10-31 | 江苏集萃药康生物科技股份有限公司 | 一种dll4人源化小鼠模型的构建方法及其应用 |
CN117467695B (zh) * | 2023-12-27 | 2024-05-03 | 南京鸿瑞杰生物医疗科技有限公司 | 过表达毕赤酵母分子伴侣提高报告蛋白分泌的方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015092024A2 (en) * | 2013-12-20 | 2015-06-25 | Cellectis | Method of engineering multi-input signal sensitive t cell for immunotherapy |
JP2015523856A (ja) * | 2012-05-25 | 2015-08-20 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフ | Rna依存性標的dna修飾およびrna依存性転写調節のための方法および組成物 |
WO2016193696A1 (en) * | 2015-06-01 | 2016-12-08 | Ucl Business Plc | Cell |
Family Cites Families (96)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4129849A1 (de) | 1991-02-14 | 1992-08-27 | Boehringer Mannheim Gmbh | Monoklonale antikoerper gegen humane pankreas-inselzellen |
US6017735A (en) * | 1997-01-23 | 2000-01-25 | Marie Curie Cancer Care | Materials and methods for intracellular transport and their uses |
GB9710809D0 (en) | 1997-05-23 | 1997-07-23 | Medical Res Council | Nucleic acid binding proteins |
AU746454B2 (en) | 1998-03-02 | 2002-05-02 | Massachusetts Institute Of Technology | Poly zinc finger proteins with improved linkers |
JP2004503463A (ja) | 1998-08-24 | 2004-02-05 | ザ ボード オブ トラスティーズ オブ ザ リーランド スタンフォード ジュニア ユニバーシティ | 免疫系媒介損傷から器官、組織および細胞を保護するための組成物および方法 |
US7013219B2 (en) | 1999-01-12 | 2006-03-14 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
US6534261B1 (en) | 1999-01-12 | 2003-03-18 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
US20030104526A1 (en) | 1999-03-24 | 2003-06-05 | Qiang Liu | Position dependent recognition of GNN nucleotide triplets by zinc fingers |
US7030215B2 (en) | 1999-03-24 | 2006-04-18 | Sangamo Biosciences, Inc. | Position dependent recognition of GNN nucleotide triplets by zinc fingers |
US6794136B1 (en) | 2000-11-20 | 2004-09-21 | Sangamo Biosciences, Inc. | Iterative optimization in the design of binding proteins |
US7229961B2 (en) | 1999-08-24 | 2007-06-12 | Cellgate, Inc. | Compositions and methods for enhancing drug delivery across and into ocular tissues |
US6593292B1 (en) | 1999-08-24 | 2003-07-15 | Cellgate, Inc. | Compositions and methods for enhancing drug delivery across and into epithelial tissues |
US7256286B2 (en) | 1999-11-30 | 2007-08-14 | The Board Of Trustees Of The Leland Stanford Junior University | Bryostatin analogues, synthetic methods and uses |
AU2002306500C1 (en) | 2001-02-16 | 2006-09-28 | Cellgate, Inc. | Transporters comprising spaced arginine moieties |
DE10211063A1 (de) | 2002-03-13 | 2003-10-09 | Axaron Bioscience Ag | Neue Verfahren zur Detektion und Analyse von Protein-Interaktionen in vivo |
US20030232410A1 (en) | 2002-03-21 | 2003-12-18 | Monika Liljedahl | Methods and compositions for using zinc finger endonucleases to enhance homologous recombination |
US20060206949A1 (en) | 2003-01-28 | 2006-09-14 | Sylvain Arnould | Custom-made meganuclease and use thereof |
CA2531698A1 (en) | 2003-07-09 | 2005-01-27 | Sentigen Biosciences, Inc. | Method for assaying protein-protein interaction |
US20070224615A1 (en) | 2003-07-09 | 2007-09-27 | Invitrogen Corporation | Methods for assaying protein-protein interactions |
FR2858235B1 (fr) | 2003-07-31 | 2006-02-17 | Lab Francais Du Fractionnement | Utilisation d'anticorps optimises en adcc pour traiter les patients faibles repondeurs |
US20110158974A1 (en) | 2005-03-15 | 2011-06-30 | Cellectis | Heterodimeric Meganucleases and Use Thereof |
EP1893627A4 (en) | 2005-05-27 | 2009-11-11 | Sentigen Biosciences Inc | MULTIPLEXARRAY SUITABLE FOR THE INVESTIGATION OF PROTEIN-PROTEIN INTERACTIONS |
US10022457B2 (en) | 2005-08-05 | 2018-07-17 | Gholam A. Peyman | Methods to regulate polarization and enhance function of cells |
DK2336362T3 (en) | 2005-08-26 | 2019-01-21 | Dupont Nutrition Biosci Aps | USE OF CRISPR-ASSOCIATED GENES (CAS) |
US8021867B2 (en) | 2005-10-18 | 2011-09-20 | Duke University | Rationally-designed meganucleases with altered sequence specificity and DNA-binding affinity |
EP1991267B1 (en) | 2006-03-03 | 2017-12-20 | Biogen MA Inc. | Methods of treating inflammatory and autoimmune diseases with natalizumab |
ATE528647T1 (de) | 2006-03-16 | 2011-10-15 | Life Technologies Corp | Verfahren zur untersuchung von protein-protein- interaktionen |
ATE530669T1 (de) | 2006-05-19 | 2011-11-15 | Danisco | Markierte mikroorganismen und entsprechende markierungsverfahren |
WO2007149807A1 (en) | 2006-06-20 | 2007-12-27 | Invitrogen Corporation | Methods for identifying modifiers of gpr1 activity |
EP2205729A2 (en) | 2007-09-27 | 2010-07-14 | Sangamo BioSciences, Inc. | Genomic editing in zebrafish using zinc finger nucleases |
US8546553B2 (en) | 2008-07-25 | 2013-10-01 | University Of Georgia Research Foundation, Inc. | Prokaryotic RNAi-like system and methods of use |
US20100076057A1 (en) | 2008-09-23 | 2010-03-25 | Northwestern University | TARGET DNA INTERFERENCE WITH crRNA |
WO2010054108A2 (en) | 2008-11-06 | 2010-05-14 | University Of Georgia Research Foundation, Inc. | Cas6 polypeptides and methods of use |
WO2010075441A1 (en) | 2008-12-22 | 2010-07-01 | Trustees Of Boston University | Modular nucleic acid-based circuits for counters, binary operations, memory, and logic |
CN102858985A (zh) * | 2009-07-24 | 2013-01-02 | 西格马-奥尔德里奇有限责任公司 | 基因组编辑方法 |
SG181601A1 (en) | 2009-12-10 | 2012-07-30 | Univ Minnesota | Tal effector-mediated dna modification |
WO2012166906A1 (en) | 2011-05-31 | 2012-12-06 | Massachusetts Institute Of Technology | Cell-directed synthesis of multifunctional nanopatterns and nanomaterials |
WO2012164565A1 (en) | 2011-06-01 | 2012-12-06 | Yeda Research And Development Co. Ltd. | Compositions and methods for downregulating prokaryotic genes |
US9732392B2 (en) | 2011-08-05 | 2017-08-15 | Northwestern University | Modular sensor architecture for cell based biosensors |
WO2013049330A1 (en) | 2011-09-28 | 2013-04-04 | The Regents Of The University Of California | Synthetic transcriptional control elements and methods of generating and using such elements |
IN2014MN00974A (ja) | 2011-12-16 | 2015-04-24 | Targetgene Biotechnologies Ltd | |
GB201122458D0 (en) | 2011-12-30 | 2012-02-08 | Univ Wageningen | Modified cascade ribonucleoproteins and uses thereof |
WO2013141680A1 (en) | 2012-03-20 | 2013-09-26 | Vilnius University | RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX |
US9637739B2 (en) | 2012-03-20 | 2017-05-02 | Vilnius University | RNA-directed DNA cleavage by the Cas9-crRNA complex |
PT3494997T (pt) | 2012-07-25 | 2019-12-05 | Massachusetts Inst Technology | Proteínas de ligação a adn indutíveis e ferramentas de perturbação do genoma e aplicações destas |
DE202013012597U1 (de) | 2012-10-23 | 2017-11-21 | Toolgen, Inc. | Zusammensetzung zum Spalten einer Ziel-DNA, umfassend eine für die Ziel-DNA spezifische guide-RNA und eine Cas-Protein-codierende Nukleinsäure oder ein Cas-Protein, sowie deren Verwendung |
US20150315576A1 (en) | 2012-11-01 | 2015-11-05 | Massachusetts Institute Of Technology | Genetic device for the controlled destruction of dna |
EP3138911B1 (en) | 2012-12-06 | 2018-12-05 | Sigma Aldrich Co. LLC | Crispr-based genome modification and regulation |
WO2014093479A1 (en) | 2012-12-11 | 2014-06-19 | Montana State University | Crispr (clustered regularly interspaced short palindromic repeats) rna-guided control of gene regulation |
ES2658401T3 (es) * | 2012-12-12 | 2018-03-09 | The Broad Institute, Inc. | Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas |
ES2576128T3 (es) | 2012-12-12 | 2016-07-05 | The Broad Institute, Inc. | Modificación por tecnología genética y optimización de sistemas, métodos y composiciones para la manipulación de secuencias con dominios funcionales |
DK2898075T3 (en) | 2012-12-12 | 2016-06-27 | Broad Inst Inc | CONSTRUCTION AND OPTIMIZATION OF IMPROVED SYSTEMS, PROCEDURES AND ENZYME COMPOSITIONS FOR SEQUENCE MANIPULATION |
EP4234696A3 (en) | 2012-12-12 | 2023-09-06 | The Broad Institute Inc. | Crispr-cas component systems, methods and compositions for sequence manipulation |
PT2921557T (pt) | 2012-12-12 | 2016-10-19 | Massachusetts Inst Technology | Engenharia de sistemas, métodos e composições guia otimizadas para a manipulação de sequências |
US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
WO2014093694A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes |
CA3081054A1 (en) | 2012-12-17 | 2014-06-26 | President And Fellows Of Harvard College | Rna-guided human genome engineering |
SI3613439T1 (sl) | 2013-02-15 | 2021-11-30 | The Regents Of The University Of California | Himerni antigenski receptor in postopki njegove uporabe |
US20160138027A1 (en) | 2013-03-14 | 2016-05-19 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of diseases and conditions associated with dysregulation of mammalian target of rapamycin complex 1 (mtorc1) |
KR101780885B1 (ko) | 2013-03-14 | 2017-10-11 | 카리부 바이오사이언시스 인코포레이티드 | 핵산-표적화 핵산의 조성물 및 방법 |
CA2906553C (en) | 2013-03-15 | 2022-08-02 | The General Hospital Corporation | Rna-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci |
US9745368B2 (en) | 2013-03-15 | 2017-08-29 | The Trustees Of The University Of Pennsylvania | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
US9234213B2 (en) | 2013-03-15 | 2016-01-12 | System Biosciences, Llc | Compositions and methods directed to CRISPR/Cas genomic engineering systems |
US10760064B2 (en) | 2013-03-15 | 2020-09-01 | The General Hospital Corporation | RNA-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci |
UY35468A (es) | 2013-03-16 | 2014-10-31 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19 |
CA2910489A1 (en) | 2013-05-15 | 2014-11-20 | Sangamo Biosciences, Inc. | Methods and compositions for treatment of a genetic condition |
EP3417880A1 (en) | 2013-06-05 | 2018-12-26 | Duke University | Rna-guided gene editing and gene regulation |
SG11201509866TA (en) * | 2013-06-06 | 2015-12-30 | Agency Science Tech & Res | Protease-responsive peptide biosensors and methods for analyte detection |
EP3011034B1 (en) | 2013-06-17 | 2019-08-07 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components |
DK3011032T3 (da) | 2013-06-17 | 2020-01-20 | Broad Inst Inc | Fremføring, modificering og optimering af systemer, fremgangsmåder og sammensætninger til målretning mod og modellering af sygdomme og forstyrrelser i postmitotiske celler |
CN105517579B (zh) | 2013-07-10 | 2019-11-15 | 哈佛大学校长及研究员协会 | 用于RNA向导的基因调节和编辑的正交Cas9蛋白 |
WO2015021426A1 (en) | 2013-08-09 | 2015-02-12 | Sage Labs, Inc. | A crispr/cas system-based novel fusion protein and its application in genome editing |
CA3109801C (en) | 2013-08-22 | 2024-01-09 | Andrew Cigan | Plant genome modification using guide rna/cas endonuclease systems and methods of use |
US9772328B2 (en) | 2013-09-12 | 2017-09-26 | The University Of Queensland | Bimolecular protease-based biosensor |
US20160237455A1 (en) | 2013-09-27 | 2016-08-18 | Editas Medicine, Inc. | Crispr-related methods and compositions |
US10822606B2 (en) | 2013-09-27 | 2020-11-03 | The Regents Of The University Of California | Optimized small guide RNAs and methods of use |
LT3066201T (lt) * | 2013-11-07 | 2018-08-10 | Editas Medicine, Inc. | Su crispr susiję būdai ir kompozicijos su valdančiomis grnr |
EP3071695A2 (en) | 2013-11-18 | 2016-09-28 | Crispr Therapeutics AG | Crispr-cas system materials and methods |
EP3074419B1 (en) | 2013-11-25 | 2018-08-29 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric antigen receptors to control hiv infection |
WO2015142661A1 (en) | 2014-03-15 | 2015-09-24 | Novartis Ag | Regulatable chimeric antigen receptor |
EP3126498A4 (en) * | 2014-03-20 | 2017-08-23 | Université Laval | Crispr-based methods and products for increasing frataxin levels and uses thereof |
AU2015236128A1 (en) | 2014-03-25 | 2016-11-10 | Editas Medicine Inc. | CRISPR/CAS-related methods and compositions for treating HIV infection and AIDS |
EP3122880B1 (en) | 2014-03-26 | 2021-05-05 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating sickle cell disease |
GB201405845D0 (en) * | 2014-04-01 | 2014-05-14 | Ucl Business Plc | Signalling system |
WO2015155686A2 (en) | 2014-04-08 | 2015-10-15 | North Carolina State University | Methods and compositions for rna-directed repression of transcription using crispr-associated genes |
WO2016011210A2 (en) | 2014-07-15 | 2016-01-21 | Juno Therapeutics, Inc. | Engineered cells for adoptive cell therapy |
DK3212789T3 (da) | 2014-10-31 | 2020-07-27 | Massachusetts Inst Technology | Massiv parallel kombinatorisk genetik til crispr |
WO2016115033A1 (en) | 2015-01-12 | 2016-07-21 | Massachusetts Institute Of Technology | Microrna combinations for anti-cancer therapeutics |
JP6784687B2 (ja) | 2015-02-24 | 2020-11-11 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 結合誘発型転写スイッチ及びその使用方法 |
US10619155B2 (en) | 2015-03-17 | 2020-04-14 | Brown University | Methods for labeling and manipulating a cellular circuit |
US20170058282A1 (en) | 2015-07-09 | 2017-03-02 | Massachusetts Institute Of Technology | Genetically engineered sensors for in vivo detection of bleeding |
JP6878408B2 (ja) | 2015-09-01 | 2021-05-26 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニアThe Regents Of The University Of California | モジュールポリペプチドライブラリならびにその作製方法及びその使用 |
WO2017044476A1 (en) | 2015-09-08 | 2017-03-16 | Massachusetts Institute Of Technology | Methods and compositions for recombinase-based genetic diversification |
CN108884456A (zh) | 2015-10-01 | 2018-11-23 | 麻省理工学院 | 生物状态机 |
MY196175A (en) | 2016-01-11 | 2023-03-20 | Univ Leland Stanford Junior | Chimeric Proteins And Methods Of Regulating Gene Expression |
BR112018013663A2 (pt) | 2016-01-11 | 2019-01-22 | Univ Leland Stanford Junior | proteínas quiméricas e métodos de imunoterapia |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015523856A (ja) * | 2012-05-25 | 2015-08-20 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフ | Rna依存性標的dna修飾およびrna依存性転写調節のための方法および組成物 |
WO2015092024A2 (en) * | 2013-12-20 | 2015-06-25 | Cellectis | Method of engineering multi-input signal sensitive t cell for immunotherapy |
WO2016193696A1 (en) * | 2015-06-01 | 2016-12-08 | Ucl Business Plc | Cell |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019504835A (ja) * | 2016-01-11 | 2019-02-21 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | キメラタンパク質および免疫治療の方法 |
JP7012645B2 (ja) | 2016-01-11 | 2022-01-28 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | キメラタンパク質および免疫治療の方法 |
WO2020179844A1 (ja) * | 2019-03-04 | 2020-09-10 | 公益財団法人東京都医学総合研究所 | Trk断片をコードする核酸構築物、及びその利用 |
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IL260532B2 (en) | 2023-12-01 |
CA3009194A1 (en) | 2017-07-20 |
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