miRNAs Enhancing Cell ProductivityThe invention relates to a nucleic acid construct comprising at least two different regions, wherein the regions are selected of a first region encoding for at least one miRNA stimulating cellular production of a biomolecule in a cell, a second region encoding for at least one miRNA and/or miRNA-inhibitor suppressing cell death, and a third region encoding for at least one miRNA and/or miRNA-inhibitor regulating cell proliferation. The invention further relates to a cell comprising a respective nucleic acid construct and to a method for increasing the yield of a biomolecule produced by a cell cultured in vitro comprising at least two steps selected of stimulating cellular production of the biomolecule, reducing cell death, and regulating proliferation.A nucleic acid construct comprising at least two different regions, wherein the regions are selected of a first region encoding for at least one miRNA stimulating cellular production of a biomolecule in a cell, the miRNA is selected from group 1,a second region encoding for at least one miRNA and/or mi-RNA inhibitor suppressing cell death, the miRNA is selected from group 2 and the miRNA-inhibitor inhibits a miRNA selected from group 3, anda third region encoding for at least one miRNA and/or miRNA-inhibitor regulating cell proliferation, the miRNA is selected from group 4 or 5 and the miRNA-inhibitor inhibits a miRNA selected from group 4 or 5,wherein group 1 consists of SEQ ID NO.: 69, 1, 2, 3, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 25, 26, 27, 28, 29, 32, 34, 37, 39, 40, 41, 42, 44, 45, 46, 47, 48, 49, 51, 52, 53, 55, 56, 57, 58, 62, 63, 66, 67, 70, 75, 76, 77, 80, 81, 82, 83, 86, 88, 90, 91, 93, 98, 99, 100, 101, 102, 103, 104, 106, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 120, 121, 128, 130, 132, 134, 136, 137, 138, 141, 142, 143, 147, 151, 152, 155, 158, 163, 165, 171, 174, 182, 183, 185, 186, 188, 190, 201, 203, 207, 211, 212, 214, 217, 222, 223, 228, 230, 233, 238, 239, 240, 254, 255, 269, 276, 278, 279, 285, and 294;group 2 consists of SEQ ID NO.: 1, 2, 3, 4, 6, 8, 9, 20, 52, 98, 5, 7, 24, 31, 33, 50, 54, 59, 60, 61, 64, 68, 71, 73, 74, 79, 85, 87, 89, 92, 94, 95 97, 145, 153, 154, 156, 159, 161, 166, 167, 168, 169, 170, 172, 175, 176, 178, 179, 180, 181, 184, 191, 192, 194, 195, 196, 197, 199, 200, 204, 205, 206, 208, 209, 210, 213, 216, 219, 220, 221, 224, 225, 226, 227, 229, 231, 236, 237, 241, 242, 243, 245, 247, 248, 251, 252, 253, 256, 257, 258, 259, 260, 262, 265, 266, 268, 271, 272, 273, 274, 277, 280, 282, 284, 289, 293, and 295;group 3 consists of SEQ ID NO.: 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 605, 607, 608, and 609;group 4 consists of SEQ ID NO.: 5, 7, 68, 79, 94, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 22, 23, 30, 35, 36, 38, 43, 65, 72, 78, 84, 96, 105, 107, 108, 119, 122, 123, 124, 125, 126, 127, 129, 131, 133, 135, 139, 140, 144, 146, 148, 149, 150, 160, 162, 164, 173, 177, 187, 189, 193, 198, 202, 215, 218, 232, 234, 235, 244, 246, 249, 250, 261, 263, 264, 267, 270, 275, 281, 283, 287, 288, and 291;and group 5 consists of SEQ ID NO.: 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, and 606.
세포 생산성을 향상시키는 마이크로RNA본 발명은 적어도 다른 두 개의 다른 영역을 포함하는 핵산 구조물에 관한 것으로, 상기 영역은 세포에서 생체분자의 세포 수준의 생산을 자극하는 적어도 하나의 miRNA을 암호화하는 제1 영역, 세포 사멸을 억제하는 적어도 하나의 miRNA 및/또는 miRNA-억제제를 암호화하는 제2 영역, 및 세포 증식을 조절하는 적어도 하나의 miRNA 및/또는 miRNA-억제제를 암호화하는 제3 영역으로부터 선택되는 것이다. 또한 본 발명은 생체 외에서 배양되는 세포에 의해 생산되는 생체분자의 생산을 증가시키는 방법에 관한 것으로, 생체분자의 세포 수준의 생산을 자극하는 단계, 세포 사멸을 감소시키는 단계, 및 세포의 증식을 조절하는 단계로부터 선택되는 적어도 두 단계를 포함한다.적어도 두 개의 다른 영역을 포함하는 핵산 구조물로서, 상기 영역은 다음으로부터 선택되는 것이고,- 세포에서 생체분자의 세포 수준의 생산을 자극하는 적어도 하나의 miRNA을 암호화하는 제1 영역으로, 상기 miRNA는 그룹 1으로부터 선택되는 것임, - 세포 사멸을 억제하는 적어도 하나의 miRNA 및/또는 miRNA-억제제를 암호화하는 제2 영역으로, 상기 miRNA는 그룹 2로부터 선택되는 것이고 상기 miRNA-억제제는 그룹 3으로부터 선택된 miRNA를 억제하는 것임, 및 - 세포 증식을 조절하는 적어도 하나의 miRNA 및/또는 miRNA-억제제를 암호화하는 제3 영역으로, 상기 miRNA는 그룹 4 또는 5로부터 선택되는 것이고 상기 miRNA-억제제는 그룹 4 또는 5로부터 선택된 miRNA를 억제하는 것임,상기 그룹 1은 서열번호 69, 1, 2, 3, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 25, 26, 27, 28, 29, 32, 34, 37, 39, 40, 41, 42, 44, 45, 46, 47, 48, 49, 51, 52, 53, 55, 56, 57, 58, 62, 63, 66, 67, 70, 75, 76, 77, 80, 81, 82, 83, 86, 88, 90, 91, 93, 98, 99, 100, 101, 102, 103, 104, 106, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 120, 121, 128, 130, 132, 134, 136, 137, 138, 141, 142, 143, 147, 151, 152, 155, 158, 163, 165, 171, 174, 182, 183, 185, 186, 188, 190, 201, 203, 207, 211, 212, 214, 217, 222, 223, 228, 230, 233, 238, 239, 240, 254, 255, 269, 276, 278, 279, 285, 및 294로 구성되어 있고; 상기 그룹 2는 서열번호 1, 2, 3, 4, 6, 8, 9, 20, 52, 98, 5, 7, 24, 31, 33, 50, 54, 59, 60, 61, 64, 68, 71, 73, 74, 79, 85, 87, 89, 92, 94, 95 97, 145, 153, 154, 156, 159, 161, 166, 167, 168, 169, 170, 172, 175, 176, 178, 179, 180, 181, 184, 191, 192, 194, 195, 196, 197, 199, 200, 204, 205, 206, 208, 209, 210, 213, 216, 219, 220, 221, 224, 225, 226, 227, 229, 231, 236, 237, 241, 242, 243, 245, 247, 248, 251, 252, 253, 256, 257, 258, 259, 260, 262, 265, 266, 268, 271, 272, 273, 274, 277, 280, 282, 284, 289, 293, 및 295로 구성되어 있고;상기 그룹 3은 서열번호 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 605, 607, 608, 및 609로 구성되어 있고, 상기 그룹 4는 서열번호 5, 7, 68, 79, 94, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 22, 23, 30, 35, 36, 38, 43, 65, 72, 78, 84, 96, 105, 107, 108, 119, 122, 123, 124, 125, 126, 127, 129, 131, 133, 135, 139, 140, 144, 146, 148, 149, 150, 160, 162, 164, 173, 177, 187, 189, 193, 198, 202, 215, 218, 232, 234, 235, 244, 246, 249, 250, 261, 263, 264, 267, 270, 275, 281, 283, 287, 288, 및 291로 구성되어 있고; 및 상기 그룹 5는 서열번호 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 및 606로 구성되어 있는 것인, 핵산 구조물.