0 10 Regulation regulation NN 11 13 of of IN 14 18 gene gene NN 19 29 expression expression NN 30 34 with with IN 35 50 double-stranded double-stranded JJ 51 67 phosphorothioate phosphorothioate NN 68 84 oligonucleotides oligonucleotide NNS 84 85 . . . 87 97 Alteration Alteration NNP 98 100 of of IN 101 105 gene gene NN 106 119 transcription transcription NN 120 122 by by IN 123 133 inhibition inhibition NN 134 136 of of IN 137 145 specific specific JJ 146 161 transcriptional transcriptional JJ 162 172 regulatory regulatory JJ 173 181 proteins protein NNS 182 184 is be VBZ 185 194 necessary necessary JJ 195 198 for for IN 199 210 determining determine VBG 211 214 how how WRB 215 220 these these DT 221 228 factors factor NNS 229 240 participate participate VBP 241 243 in in IN 244 252 cellular cellular JJ 253 268 differentiation differentiation NN 268 269 . . . 270 273 The the DT 274 283 functions function NNS 284 286 of of IN 287 292 these these DT 293 301 proteins protein NNS 302 305 can can MD 306 308 be be VB 309 320 antagonized antagonize VBN 321 323 by by IN 324 331 several several JJ 332 339 methods method NNS 339 340 , , , 341 345 each each DT 346 350 with with IN 351 359 specific specific JJ 360 371 limitations limitation NNS 371 372 . . . 373 383 Inhibition Inhibition NNP 384 386 of of IN 387 404 sequence-specific sequence-specific JJ 405 416 DNA-binding dna-binding JJ 417 425 proteins protein NNS 426 429 was be VBD 430 438 achieved achieve VBN 439 443 with with IN 444 459 double-stranded double-stranded JJ 460 461 ( ( ( 461 463 ds d NNS 463 464 ) ) ) 465 481 phosphorothioate phosphorothioate NN 482 498 oligonucleotides oligonucleotide NNS 499 503 that that WDT 504 513 contained contain VBD 514 521 octamer octamer NN 522 524 or or CC 525 530 kappa kappa NN 531 532 B B NNP 533 542 consensus consensus NN 543 552 sequences sequence NNS 552 553 . . . 554 557 The the DT 558 574 phosphorothioate phosphorothioate NN 575 591 oligonucleotides oligonucleotide NNS 592 604 specifically specifically RB 605 610 bound bind VBD 611 617 either either CC 618 625 octamer octamer NN 626 639 transcription transcription NN 640 646 factor factor NN 647 649 or or CC 650 657 nuclear nuclear JJ 658 664 factor factor NN 665 666 ( ( ( 666 675 NF)-kappa NF)-kappa NNP 676 678 B. B. NNP 679 682 The the DT 683 691 modified modified JJ 692 708 oligonucleotides oligonucleotide NNS 709 720 accumulated accumulate VBN 721 723 in in IN 724 729 cells cell NNS 730 734 more more RBR 735 746 effectively effectively RB 747 751 than than IN 752 760 standard standard JJ 761 763 ds d NNS 764 780 oligonucleotides oligonucleotide NNS 781 784 and and CC 785 794 modulated modulate VBN 795 799 gene gene NN 800 810 expression expression NN 811 813 in in IN 814 815 a a DT 816 824 specific specific JJ 825 831 manner manner NN 831 832 . . . 833 850 Octamer-dependent octamer-dependent JJ 851 861 activation activation NN 862 864 of of IN 865 866 a a DT 867 875 reporter reporter NN 876 883 plasmid plasmid NN 884 886 or or CC 887 895 NF-kappa NF-kappa NNP 896 907 B-dependent b-dependent JJ 908 918 activation activation NN 919 921 of of IN 922 925 the the DT 926 931 human human JJ 932 948 immunodeficiency immunodeficiency NN 949 954 virus virus NN 955 956 ( ( ( 956 959 HIV HIV NNP 959 960 ) ) ) 961 969 enhancer enhancer NN 970 973 was be VBD 974 983 inhibited inhibit VBN 984 988 when when WRB 989 992 the the DT 993 1004 appropriate appropriate JJ 1005 1021 phosphorothioate phosphorothioate NN 1022 1037 oligonucleotide oligonucleotide NN 1038 1041 was be VBD 1042 1047 added add VBN 1048 1050 to to TO 1051 1052 a a DT 1053 1064 transiently transiently RB 1065 1076 transfected transfecte VBN 1077 1078 B B NNP 1079 1083 cell cell NN 1084 1088 line line NN 1088 1089 . . . 1090 1098 Addition addition NN 1099 1101 of of IN 1102 1118 phosphorothioate phosphorothioate NN 1119 1135 oligonucleotides oligonucleotide NNS 1136 1140 that that WDT 1141 1150 contained contain VBD 1151 1154 the the DT 1155 1162 octamer octamer NN 1163 1172 consensus consensus NN 1173 1175 to to TO 1176 1182 Jurkat Jurkat NNP 1183 1184 T t NN 1185 1193 leukemia leukemia NN 1194 1199 cells cell NNS 1200 1209 inhibited inhibit VBD 1210 1223 interleukin-2 interleukin-2 NN 1224 1225 ( ( ( 1225 1229 IL-2 il-2 NN 1229 1230 ) ) ) 1231 1240 secretion secretion NN 1241 1243 to to TO 1244 1245 a a DT 1246 1252 degree degree NN 1253 1260 similar similar JJ 1261 1263 to to TO 1264 1268 that that DT 1269 1277 observed observe VBN 1278 1282 with with IN 1283 1284 a a DT 1285 1292 mutated mutate VBN 1293 1300 octamer octamer NN 1301 1305 site site NN 1306 1308 in in IN 1309 1312 the the DT 1313 1317 IL-2 il-2 NN 1318 1326 enhancer enhancer NN 1326 1327 . . . 1328 1331 The the DT 1332 1334 ds d NNS 1335 1351 phosphorothioate phosphorothioate VBP 1352 1368 oligonucleotides oligonucleotide NNS 1369 1377 probably probably RB 1378 1385 compete compete VBP 1386 1389 for for IN 1390 1397 binding binding NN 1398 1400 of of IN 1401 1409 specific specific JJ 1410 1423 transcription transcription NN 1424 1431 factors factor NNS 1432 1435 and and CC 1436 1439 may may MD 1440 1447 provide provide VB 1448 1458 anti-viral anti-viral JJ 1458 1459 , , , 1460 1477 immunosuppressive immunosuppressive JJ 1477 1478 , , , 1479 1481 or or CC 1482 1487 other other JJ 1488 1499 therapeutic therapeutic JJ 1500 1507 effects effect NNS 1507 1508 . . .