Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor
AssigneeThe Trustees of the University of Pennsylvania
InventorsGuangping Gao, James M. Wilson, Mauricio R. Alvira
Life of this patent
Estimating the term…
Abstract
Sequences of a serotype 8 adeno-associated virus 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. rAAV8-mediated delivery of therapeutic and immunogenic genes, including Factor VIII, is also provided.
Claims26
An isolated adeno-associated virus (AAV) comprising an AAV capsid having an amino acid sequence of AAV8, amino acids 1 to 737 of SEQ ID NO:2.
The isolated AAV according to claim 2, wherein said virus has the nucleic acid sequence of SEQ ID NO:1.
A protein comprising an AAV8 protein or a fragment thereof selected from the group consisting of:
- (a) an AAV8 capsid protein or fragment thereof, selected from the group consisting of:
- vp1capsid protein, amino acids (aa) 1 to 737 ;
- vp2 capsid protein, aa 138 to 737;
- vp3 capsid protein, aa 203 to 737;
- a fragment encompassing hypervariable region (HVR)1 through 12 or a smaller fragment thereof 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 413to417;
- aa 449to478;
- aa 494to525;
- aa 534to571;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 AAV8, SEQ ID NO:2;
- and
- (b) an AAV8 rep protein or fragment thereof selected from the group consisting of:
- aa 1 to 625;
- aa 1 to 102;
- aa 103 to 140;
- aa 141 to 173;
- aa 174 to 226;
- aa 227 to 275;
- aa 276 to 374;
- aa 375 to 383;
- aa 384 to 446;
- aa 447 to 542;
- aa 543 to 555;
- and aa 556 to 625, of SEQ ID NO:
- 3 .
A recombinant adeno-associated viral (AAV) vector comprising an AAV8 capsid and a nucleotide sequence encoding a Factor VIII transgene operably linked to expression control elements.
A method of treating hemophilia in a mammal comprising:
- administering a rAAV having a serotype 8 capsid to a mammal under conditions that result in the expression of the Factor VIII protein at a level that provides a therapeutic effect in said mammal.
Dependencies are inferred from the claim text.