Adeno-associated virus (aav) clades, sequences, vectors containing same, and uses therefor
AssigneeThe Trustees of the University of Pennsylvania
InventorsJames M. Wilson, Guangping Gao, Mauricio R. Alvira, Luc H. Vandenberghe
Life of this patent
Estimating the term…
Abstract
Sequences of novel adeno-associated virus capsids and vectors and host cells containing these sequences are provided. Also described are methods of using such host cells and vectors in production of rAAV particles. AAV-mediated delivery of therapeutic and immunogenic genes using the vectors of the invention is also provided.
Claims15
An AAV comprising an AAV9 capsid, wherein the AAV9 capsid comprises an amino acid sequence having at least 95% identity with amino acids 203 to 736 of SEQ ID NO:
- 123, and wherein said AAV further comprises a minigene having AAV inverted terminal repeats and a transgene comprising a heterologous gene operably linked to regulatory sequences which direct expression of the heterologous gene in an host cell.
An adeno-associated virus (AAV) comprising an AAV capsid selected from the group consisting of:
- serotype hu.35, amino acids 204 to 734 of SEQ ID NO:
- 186;
- serotype hu.37, amino acids 204 to 738 of SEQ ID NO:
- 88;
- serotype pi.2, amino acids 203 to 731 of SEQ ID NO:
- 95;
- serotype rh.64, SEQ ID NO:
- 99;
- and serotype rh.65R2, SEQ ID NO:
- 233;
- and wherein the AAV further comprises a minigene having AAV inverted terminal repeats and a heterologous gene operably linked to regulatory sequences which direct its expression in a host cell.
An adeno-associated virus (AAV) clade F comprising AAV9, AAV hu.14/AAV9 (SEQ ID Nos:
- 3 and 123), hu.31 (SEQ ID NOs:
- 1 and 121) and hu.32 (SEQ ID Nos:
- 2 and 122), wherein each member of said AAV clade is phylogenetically related as determined using a Neighbor-Joining heuristic by a bootstrap value of at least 75% per 1000 isolates and a Poisson correction distance measurement of no more than 0.05.
A composition comprising a pharmaceutical carrier and a protein comprising an AAV9/HU.14 capsid protein or a fragment thereof selected from the group consisting of:
- vp1 capsid protein, amino acids (aa) 1 to 736, SEQ ID NO:123;
- an AAV capsid comprising a vp2 capsid protein, aa 138 to 736, SEQ ID NO:
- 123;
- an AAV capsid comprising a vp3 capsid protein, aa 203 to 736, SEQ ID NO:
- 123;
- an AAV capsid comprising a fragment encompassing at least one hypervariable region (HVR)1 through 12 selected the group consisting of:
- aa 146 to 152;
- aa 182 to 187;
- aa 262 to 264;
- aa 263 to 266;
- aa 263 to 266;
- aa 381 to 383;
- 383 to 385;
- aa 450 to 474;
- aa 451 to 475;
- aa 490 to 495;
- aa 491 to 496;
- aa500 to 504;
- aa 501 to 505;
- aa 514 to 522;
- aa 533 to 554;
- aa 534 to 555;
- aa 581 to 594;
- aa 583 to 596;
- aa 658 to 667;
- aa 660 to 669;
- and aa 705 to 719;
- aa 707 to 723;
- aa 24 to 42, aa 25 to 28;
- aa 81 to 85;
- aa133 to 165;
- aa 134 to 165;
- aa 137 to 143;
- aa 154 to 156;
- aa 194 to 208;
- aa 261 to 274;
- aa 262 to 274;
- aa 171 to 173;
- aa 185 to 198;
- aa 413 to 417;
- aa 449 to 478;
- aa 494 to 525;
- aa 534 to 571;
- aa 581 to 601;
- aa 660 to 671;
- aa 709 to 723;
- and
- aa 1 to 184, aa 199 to 259;
- aa 274 to 446;
- aa 603 to 659;
- aa 670 to 706;
- aa 724 to 736;
- aa 185 to 198;
- aa 260 to 273;
- aa447 to 477;
- aa495 to 602;
- aa603 to 659;
- aa 660 to 669;
- and aa707 to 723, wherein the amino acid numbers are those of the AAV2 capsid, SEQ ID NO:4 and corresponding regions in the capsid of AAV9/HU.14, SEQ ID NO:123.
Dependencies are inferred from the claim text.