Adeno-Associated Virus Factor VIII Vectors
The invention provides completely packaged adeno-associated virus (AAV) Factor VIII (FVIII) vectors. This invention also provides completely packaged AAV FVIII vectors with high expression activity.
1 . (canceled)
2 . An adeno-associated virus (AAV) Factor VIII (FVIII) comprising a nucleotide sequence selected from the group consisting of:
i. the Proto 1 sequence set forth in SEQ ID NO: 1,
ii. the Proto 1S sequence set forth in SEQ ID NO: 2,
iii. the Proto 2S sequence set forth in SEQ ID NO: 3,
iv. the Proto 3S sequence set forth in SEQ ID NO: 4,
v. the Proto 4 sequence set forth in SEQ ID NO: 5,
vi. the Proto 5 sequence set forth in SEQ ID NO: 6,
vii. the Proto 6 sequence set forth in SEQ ID NO: 7,
viii. the Proto 7 sequence set forth in SEQ ID NO: 8,
ix. the Construct 100ATG sequence set forth in SEQ ID NO: 9,
x. the Construct 100ATG bGH poly A sequence set forth in SEQ ID NO: 10,
xi. the Construct 100ATG short bGH polyA sequence set forth in SEQ ID NO: 11,
xii. the Construct 103ATG sequence set forth in SEQ ID NO: 12,
xiii. the Construct 103ATG short bGH poly A sequence set forth in SEQ ID NO: 13,
xiv. the Construct 105ATG bGH poly A sequence set forth in SEQ ID NO: 14,
xv. the Construct DC172ATG FVIII sequence set forth in SEQ ID NO: 15,
xvi. the Construct DC172 ATG FVIII hAAT sequence set forth in SEQ ID NO: 16,
xvii. the Construct DC172 2×HCR ATG FVIII sequence set forth in SEQ ID NO: 17,
xviii. the Construct DC172 2×HCR ATG FVIII hAAT sequence set forth in SEQ ID NO: 18,
xix. the Construct 2× SerpinA hAAT ATG FVIII sequence set forth in SEQ ID NO: 19,
xx. the Construct 2× SerpinA hAAT ATG FVIII 2× μ-globulin enhancer sequence set forth in SEQ ID NO: 20,
xxi. the Construct 100ATG short polyA 2× μ-globulin enhancer sequence set forth in SEQ ID NO: 21,
xxii. the Construct Factor VIII-BMN001 sequence set forth in SEQ ID NO: 22,
xxiii. the Construct Factor VIII-BMN002 sequence set forth in SEQ ID NO: 23,
xxiv. the Construct 99 sequence set forth in SEQ ID NO: 24,
xxv. the Construct 100 sequence set forth in SEQ ID NO: 25,
xxvi. the Construct 100 reverse orientation sequence set forth in SEQ ID NO: 26,
xxvii. the Construct 100AT sequence set forth in SEQ ID NO: 27,
xxviii. the Construct 100AT 2× MG sequence set forth in SEQ ID NO: 28,
xxix. the Construct 100AT 2× MG polyA sequence set forth in SEQ ID NO: 29,
xxx. the Construct 100AT 2× MG (reverse) bGH polyA sequence set forth in SEQ ID NO: 30,
xxxi. the Construct 100 bGH polyA sequence set forth in SEQ ID NO: 31,
xxxii. the Construct 100-400 sequence set forth in SEQ ID NO: 32,
xxxiii. the Construct 101 sequence set forth in SEQ ID NO: 33,
xxxiv. the Construct 102 sequence set forth in SEQ ID NO: 34,
xxxv. the Construct 103 sequence set forth in SEQ ID NO: 35,
xxxvi. the Construct 103 reverse orientation sequence set forth in SEQ ID NO: 36,
xxxvii. the Construct 103AT sequence set forth in SEQ ID NO: 37,
xxxviii. the Construct 103AT 2× MG sequence set forth in SEQ ID NO: 38,
xxxix. the Construct 103AT 2× MG polyA sequence set forth in SEQ ID NO: 39,
xl. the Construct 103 bGH polyA sequence set forth in SEQ ID NO: 40,
xli. the Construct 104 sequence set forth in SEQ ID NO: 41,
xlii. the Construct 105 sequence set forth in SEQ ID NO: 42,
xliii the Construct 106 sequence set forth in SEQ ID NO: 43,
xliv. the Construct 106AT sequence set forth in SEQ ID NO: 44, and
xlv. the Construct 2× Serpin A hAAT sequence set forth in SEQ ID NO: 45.
3 . A method of producing a recombinant adeno-associated virus (AAV) particle comprising
A) culturing a cell that has been transfected with a AAV vector of claim 2 ; and
B) recovering recombinant AAV particle from the supernatant of the transfected cell.
4 . A viral particle comprising the viral vector of claim 2 .
5 . A cell comprising the viral vector of claim 2 .
6 . A method of treating a patient suffering from hemophilia A comprising administering to the patient an effective amount of an AAV FVIII vector of claim 2 .
7 . (canceled)
8 . A composition comprising an AAV FVIII vector of claim 2 .