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US 12,618,082 B2Granted
Engineered muscle targeting compositions
AssigneesThe Broad Institute, Inc., President and Fellows of Harvard College, Massachusetts Institute of Technology
InventorsPardis Sabeti, Mohammadsharif Tabebordbar, Simon Ye, Kim Lagerborg, Alexandra Stanton, Amy Wagers
Life of this patent
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Abstract
Described herein are muscle-specific targeting moieties and compositions including the muscle specific targeting motifs. Also described herein are uses of the muscle-specific targeting motifs and compositions including the muscle specific targeting moieties. In some embodiments, the muscle-specific targeting moieties and compositions including the muscle specific targeting moieties can be used to direct delivery of a cargo to a muscle cell.
Claims28
An engineered adeno-associated virus (AAV) capsid polypeptide comprising:
- an n-mer motif inserted in a surface variable region VR-VIII of the engineered AAV capsid polypeptide,
- wherein the n-mer motif comprises the amino acid sequence of any one of SEQ ID NOs:
- 2-7, 20-21, 28-33, 49, 51, 53, 55, 57, 59, 61, 64, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 91, 94, 96, 100, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 158, 160, 163, 166, 168, 170, 172, 174, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 199, 201, 203, 205, 207, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 282, 284, 286, 288, 290, 293, 295, 297, 299, 301, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 327, 329, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 378, 380, 382, 384, 386, 388, 390, 392, 394, 396, 398, 401, 404, 406, 408, 411, 413, 418, 420, 423, 426, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456, 458, 460, 462, 464, 466, 468, 470, 472, 476, 478, 480, 482, 484, 487, 489, 492, 494, 497, 499, 501, 504, 506, 508, 510, 512, 514, 516, 519, 521, 523, 526, 529, 531, 533, 535, 538, 542, 544, 546, 548, 551, 553, 555, 558, 561, 563, 565, 567, 570, 572, 574, 576, 579, 582, 584, 586, 588, 591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625, 628, 630, 632, 634, 636, 638, 640, 642, 644, 646, 648, 651, 653, 655, 657, 659, 661, 663, 665, 667, 669, 672, 674, 676, 678, 680, 682, 684, 686, 688, 690, 692, 694, 696, 698, 700, 703, 707, 709, 711, 713, 715, 717, 720, 723, 726, 728, 731, 733, 735, 737, 739, 741, 743, 745, 747, 749, 751, 754, 756, 758, 760, 763, and 767.
A vector system comprising:
- a vector comprising:
- (a) one or more polynucleotides each encoding one or more engineered adeno-associated virus (AAV) capsid polypeptides, or
- (b) one or more polynucleotides encoding one or more engineered AAV capsid polypeptides and a cargo,
- wherein each of the one or more polypeptides of (a) and (b) comprises an n-mer motif inserted in a surface variable region VR-VIII of the one or more engineered AAV capsid polypeptides,
- wherein the n-mer motif comprises the amino acid sequence of any one of SEQ ID NO:
- 2-7, 20-21, 28-33, 49, 51, 53, 55, 57, 59, 61, 64, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 91, 94, 96, 100, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 158, 160, 163, 166, 168, 170, 172, 174, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 199, 201, 203, 205, 207, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 282, 284, 286, 288, 290, 293, 295, 297, 299, 301, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 327, 329, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 378, 380, 382, 384, 386, 388, 390, 392, 394, 396, 398, 401, 404, 406, 408, 411, 413, 418, 420, 423, 426, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456, 458, 460, 462, 464, 466, 468, 470, 472, 476, 478, 480, 482, 484, 487, 489, 492, 494, 497, 499, 501, 504, 506, 508, 510, 512, 514, 516, 519, 521, 523, 526, 529, 531, 533, 535, 538, 542, 544, 546, 548, 551, 553, 555, 558, 561, 563, 565, 567, 570, 572, 574, 576, 579, 582, 584, 586, 588, 591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625, 628, 630, 632, 634, 636, 638, 640, 642, 644, 646, 648, 651, 653, 655, 657, 659, 661, 663, 665, 667, 669, 672, 674, 676, 678, 680, 682, 684, 686, 688, 690, 692, 694, 696, 698, 700, 703, 707, 709, 711, 713, 715, 717, 720, 723, 726, 728, 731, 733, 735, 737, 739, 741, 743, 745, 747, 749, 751, 754, 756, 758, 760, 763, and 767;
- and
- a regulatory element is operatively coupled to one or more polynucleotide(s), the cargo, or both.
5 more elements
An engineered AAV particle comprising
- a cargo polynucleotide comprising a mini- or micro-dystrophin gene comprising spectrin-like repeats 1, 2, 3, and 24, and
- an engineered AAV capsid polypeptide comprising
- a muscle-specific targeting moiety comprising
- an n-mer motif of any one of SEQ ID NOs:
- 28, 29, 30, 31, 32 and 33 inserted between any two amino acids between amino acids 581-593 in an AAV9 capsid polypeptide of SEQ ID NO:
- 1, or an analogous position in an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV rh.74, or an AAV rh.10 capsid polypeptide.
3 more elements
Dependencies are inferred from the claim text.