| 主权项 |
1. A protein comprising an engineered zinc finger DNA-binding domain, wherein the engineered zinc finger DNA-binding domain comprises four, five or six zinc finger DNA recognition regions designated and ordered F1 to F4, F1 to F5 or F1 to F6 from N-terminus to C-terminus and further wherein the engineered zinc finger DNA-binding domain comprises the zinc finger DNA recognition regions selected from the group consisting of:
(i) F1: QSSHLTR (SEQ ID NO:1);
F2: RSDHLTT (SEQ ID NO:2);F3: RSDTLSQ (SEQ ID NO:3);F4: RSADLSR (SEQ ID NO:4);F5: QSSDLSR (SEQ ID NO:5); andF6: RSDALTQ (SEQ ID NO:6), wherein the protein binds to the target site set forth in SEQ ID NO:97 in an endogenous human leukocyte antigen (HLA) A2 gene; (ii) F1: QKTHLAK (SEQ ID NO:7);
F2: RSDTLSN (SEQ ID NO:8);F3: RKDVRIT (SEQ ID NO:9);F4: RSDHLST (SEQ ID NO:10); andF5: DSSARKK (SEQ ID NO:11), wherein the protein binds to the target site set forth in SEQ ID NO:98 in an endogenous HLA A2 gene; (iii) F1: QNAHRKT (SEQ ID NO:12);
F2: RSDSLLR (SEQ ID NO:13);F3: RNDDRKK (SEQ ID NO:14);F4: RSDHLST (SEQ ID NO:10); andF5: DSSARKK (SEQ ID NO:11), wherein the protein binds to the target site set forth in SEQ ID NO:99 in an endogenous HLA A2 gene; (iv) F1: DRSHLSR (SEQ ID NO:15);
F2: RSDDLTR (SEQ ID NO:16);F3: DRSDLSR (SEQ ID NO:17); andF4: QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:100 in an endogenous HLA A3 gene; (v) F1: DRSALSR (SEQ ID NO:19);
F2: QSSDLRR (SEQ ID NO:20);F3: DRSALSR (SEQ ID NO:19);F4: DRSHLAR (SEQ ID NO:21);F5: RSDDLSK (SEQ ID NO:22); andF6: DRSHLAR (SEQ ID NO:21), wherein the protein binds to the target site set forth in SEQ ID NO:101 in an endogenous HLA A3 gene; (vi) F1: SSELLNE (SEQ ID NO:23);
F2: TSSHLSR (SEQ ID NO:24);F3: QSGDRNK (SEQ ID NO:25);F4: RSANLAR (SEQ ID NO:26); andF5: RSDNLRE (SEQ ID NO:27), wherein the protein binds to the target site set forth in SEQ ID NO:102 in an endogenous HLA B gene; (vii) F1: QSGDLTR (SEQ ID NO:28);
F2: RSDDLTR (SEQ ID NO:16);F3: DQSTLRN (SEQ ID NO:29);F4: DRSNLSR (SEQ ID NO:30); andF5: DAFTRTR (SEQ ID NO:31), wherein the protein binds to the target site set forth in SEQ ID NO:103 in an endogenous HLA B gene; (viii) F1: RSDNLSE (SEQ ID NO:32);
F2: ASKTRKN (SEQ ID NO:33);F3: TSGNLTR (SEQ ID NO:34); andF4: RSDALAR (SEQ ID NO:35), wherein the protein binds to the target site set forth in SEQ ID NO:104 in an endogenous HLA B gene; (ix) F1: DRSALSR (SEQ ID NO:19);
F2: QSGNLAR (SEQ ID NO:36);F3: DRSALSR (SEQ ID NO:19);F4: QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:105 in an endogenous HLA B gene; (x) F1: RSDNLSE (SEQ ID NO:32);
F2: ASKTRKN (SEQ ID NO:33);F3: QSGHLSR (SEQ ID NO:18);F4: TSGHLSR (SEQ ID NO:37); andF5: QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:106 in an endogenous HLA B gene; (xi) F1: RSADLTR (SEQ ID NO:38);
F2: QSGDLTR (SEQ ID NO:28);F3: QSGNLAR (SEQ ID NO:36); andF4: QSGDLTR (SEQ ID NO:28), wherein the protein binds to the target site set forth in SEQ ID NO:107 in an endogenous HLA B gene; (xii) F1: QSGHLSR (SEQ ID NO:18);
F2: RSDHLST (SEQ ID NO:10);F3: QSADRTK (SEQ ID NO:39);F4: TSGSLSR (SEQ ID NO:40); andF5: QSADRTK (SEQ ID NO:39), wherein the protein binds to the target site set forth in SEQ ID NO:108 in an endogenous HLA C gene; (xiii) F1: QSGDLTR (SEQ ID NO:28);
F2: RSDHLST (SEQ ID NO:10);F3: QSADRTK (SEQ ID NO:39);F4: RSDNLSA (SEQ ID NO:41); andF5: RSDNRTT (SEQ ID NO:42), wherein the protein binds to the target site set forth in SEQ ID NO:109 in an endogenous HLA C gene; (xiv) F1: QRSNLVR (SEQ ID NO:43);
F2: DRSALAR (SEQ ID NO:44);F3: QSSDLRR (SEQ ID NO:20);F4: RSDDLTR (SEQ ID NO:16); andF5: RSDDLTR (SEQ ID NO:16), wherein the protein binds to the target site set forth in SEQ ID NO:110 in an endogenous HLA C gene; (xv) F1: RSDDLTR (SEQ ID NO:16);
F2: DRSDLSR (SEQ ID NO:17);F3: QSGHLSR (SEQ ID NO:18);F4: RSDHLSA (SEQ ID NO:45); andF5: ESRYLMV (SEQ ID NO:46), wherein the protein binds to the target site set forth in SEQ ID NO:111 in an endogenous HLA C gene; (xvi) F1: RSDHLST (SEQ ID NO:10);
F2: DNANRTK (SEQ ID NO:47);F3: QSGDLTR (SEQ ID NO:28);F4: RSDALST (SEQ ID NO:48); andF5: ASSNRKT (SEQ ID NO:49), wherein the protein binds to the target site set forth in SEQ ID NO:112 in an endogenous DBP2 gene; (xvii) F1: TSGNLTR (SEQ ID NO:34);
F2: DRSDLSR (SEQ ID NO:17);F3: RSDNLSE (SEQ ID NO:32);F4: RSANLTR (SEQ ID NO:50); andF5: QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:113 in an endogenous DBP2 gene; (xviii) F1: RSDNLSE (SEQ ID NO:32);
F2: TSGSLTR (SEQ ID NO:51);F3: TSGHLSR (SEQ ID NO:37);F4: RSDNLSQ (SEQ ID NO:52); andF5: ASNDRKK (SEQ ID NO:53), wherein the protein binds to the target site set forth in SEQ ID NO:114 in an endogenous DRA gene; (xix) F1: RSDNLSR (SEQ ID NO:54);
F2: DNNARIN (SEQ ID NO:55);F3: RSDSLSV (SEQ ID NO:56);F4: QNQHRIN (SEQ ID NO:57); andF5: RSDHLSR (SEQ ID NO:58), wherein the protein binds to the target site set forth in SEQ ID NO:115 in an endogenous DRA gene; (xx) F1: DSSDRKK (SEQ ID NO:59);
F2: DRSHLTR (SEQ ID NO:60);F3: RSDALAR (SEQ ID NO:35);F4: QSSDLSR (SEQ ID NO:5); andF5: RSDNLTT (SEQ ID NO:61), wherein the protein binds to the target site set forth in SEQ ID NO:116 in an endogenous transporter associated with antigen processing 1 (TAP1) gene; (xxi) F1: RSANLAR (SEQ ID NO:26);
F2: QSGHLSR (SEQ ID NO:18);F3: TSGNLTR (SEQ ID NO:34);F4: QSGALVI (SEQ ID NO:62);F5: RSDHLSE (SEQ ID NO:63); andF6: RKHDRTK (SEQ ID NO:64), wherein the protein binds to the target site set forth in SEQ ID NO:117 in an endogenous TAP1 gene; (xxii) F1: QSSDLSR (SEQ ID NO:5);
F2: QSGDLTR (SEQ ID NO:28);F3: QSSHLTR (SEQ ID NO:1):F4: RSDDRKT (SEQ ID NO:65);F5: TSGNLTR (SEQ ID NO:34); andF6: RSDDLTR (SEQ ID NO:16), wherein the protein binds to the target site set forth in SEQ ID NO:118 in an endogenous transporter associated with antigen processing 2(TAP2) gene; (xxiii) F1: RSDNLST (SEQ ID NO:66);
F2: RSDALAR (SEQ ID NO:35);F3: RSDVLSA (SEQ ID NO:67);F4: DRSNRIK (SEQ ID NO:68);F5: RREDLIT (SEQ ID NO:69); andF6: TSSNLSR (SEQ ID NO:70), wherein the protein binds to the target site set forth in SEQ ID NO:119 in an endogenous TAP2 gene; (xxiv) F1: RSDNLSE (SEQ ID NO:32);
F2: KRCNLRC (SEQ ID NO:71);F3: DRSDLSR (SEQ ID NO:17);F4: QTTHRNR (SEQ ID NO:72);F5: DRSDLSR (SEQ ID NO:17), andF6: QSSTRAR (SEQ ID NO:73), wherein the protein binds to the target site set forth in SEQ ID NO:120 in an endogenous tapasin gene; (xxv) F1: QSSDLR (SEQ ID NO:5);
F2: RSDNLTR (SEQ ID NO:74);F3: QSSHLTR (SEQ ID NO:1);F4: QSSDLTR (SEQ ID NO:75);F5: RSDNLAR (SEQ ID NO:76); andF6: QKVNLMS (SEQ ID NO:77), wherein the protein binds to the target site set forth in SEQ ID NO:121 in an endogenous tapasin gene; (xxvi) F1: TSGNLTR (SEQ ID NO:34);
F2: LSQDLNR (SEQ ID NO:78);F3: RSDSLSA (SEQ ID NO:79);F4: DRSHLAR (SEQ ID NO:21);F5: RSDHLST (SEQ ID NO:10); andF6: QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:122 in an endogenous tapasin gene; (xxvii) F1: RSDDLTR (SEQ ID NO:16);
F2: SSSNLTK (SEQ ID NO:80);F3: TSGSLSR (SEQ ID NO:40);F4: QSGDLTR (SEQ ID NO:28);F5: RSDHLSE (SEQ ID NO:63); andF6: RNRDRIT (SEQ ID NO:81), wherein the protein binds to the target site set forth in SEQ ID NO:123 in an endogenous tapasin gene; (xxviii) F1: RSDDLTR (SEQ ID NO:16);
F2: RSDHLSE (SEQ ID NO:63);F3: NSRNRKT (SEQ ID NO:82);F4: RSDNLSQ (SEQ ID NO:52); andF5: ASNDRKK (SEQ ID NO:53), wherein the protein binds to the target site set forth in SEQ ID NO:124 in an endogenous class 2 transactivator (CTIIA) gene; (xxvix) F1: RSDDLSR (SEQ ID NO:83);
F2: RNDDRKK (SEQ ID NO:14);F3: DRSDLSR (SEQ ID NO:17);F4: RSDHLSE (SEQ ID NO:63); andF5: ARSTRTN (SEQ ID NO:84), wherein the protein binds to the target site set forth in SEQ ID NO:125 in an endogenous CTIIIA gene; (xxx) F1: TSGNLTR (SEQ ID NO:34);
F2: QSGNLAR (SEQ ID NO:36);F3: RSDHLTQ (SEQ ID NO:85);F4: ASMALNE (SEQ ID NO:86); andF5: TSSNLSR (SEQ ID NO:70), wherein the protein binds to the target site set forth in SEQ ID NO:126 in an endogenous regulatory factor X protein 5 (RXF5) gene; (xxxi) F1: RSDVLSE (SEQ ID NO:87);
F2: RNQHRKT (SEQ ID NO:88);F3: RSDHLST (SEQ ID NO:10);F4: QSSDLRR (SEQ ID NO:20);F5: RSDNLST (SEQ ID NO:66); andF6: RSADRKN (SEQ ID NO:89), wherein the protein binds to the target site set forth in SEQ ID NO:127 in an endogenous RXF5 gene; (xxxii) F1: QSGDLTR (SEQ ID NO:28);
F2: QWGTRYR (SEQ ID NO:90);F3: ERGTLAR (SEQ ID NO:91);F4: RSDNLRE (SEQ ID NO:27);F5: QSGDLTR (SEQ ID NO:28); andF6: TSGSLTR (SEQ ID NO:51), wherein the protein binds to the target site set forth in SEQ ID NO:128 in an endogenous T-cell receptor alpha (TRAC) gene; (xxxiii) F1: QSGDLTR (SEQ ID NO:28);
F2: WRSSLAS (SEQ ID NO:92);F3: QSGDLTR (SEQ ID NO:28);F4: HKWVLRQ (SEQ ID NO:93); andF5: DRSNLTR (SEQ ID NO:94), wherein the protein binds to the target site set forth in SEQ ID NO:129 in an endogenous TRAC gene; (xxxiv)F1: RSDVLSA (SEQ ID NO:67);
F2: DRSNRIK (SEQ ID NO:68);F3: RSDVLSE (SEQ ID NO:87);F4: QSGNLAR (SEQ ID NO:36); andF5: QSGSLTR (SEQ ID NO:95), wherein the protein binds to the target site set forth in SEQ ID NO:130 in an endogenous T-cell receptor beta (TRBC) gene; and (xxxv) F1: RSDHLST (SEQ ID NO:10);
F2: RSDNLTR (SEQ ID NO:74);F3: DRSNLSR (SEQ ID NO:30);F4: TSSNRKT (SEQ ID NO:96);F5: RSANLAR (SEQ ID NO:26); andF6: RNDDRKK (SEQ ID NO:14), wherein the protein binds to the target site set forth in SEQ ID NO:131 in an endogenous TRBC gene. |
