| CPC C12N 7/00 (2013.01) [A61K 9/0046 (2013.01); A61K 48/005 (2013.01); A61P 27/16 (2018.01); C07K 16/22 (2013.01); C12N 2750/14143 (2013.01)] | 16 Claims |
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1. A method of delivering anti-VEGF antibody to an inner ear of a mammal, said method comprising:
delivering via intra-cochlear administration an adeno-associated virus (AAV) vector into the inner ear of the mammal, and
wherein the AAV vector comprises a nucleotide sequence comprising:
(i) a first coding sequence that encodes a first polypeptide comprising an antibody heavy chain variable domain operably linked to a first signal peptide, wherein the first coding sequence comprises the nucleotide sequence of SEQ ID NO: 52;
(ii) a second coding sequence that encodes a second polypeptide comprising an antibody light chain variable domain operably linked to a second signal peptide, wherein the second coding sequence comprises the nucleotide sequence of SEQ ID NO: 53; and
(iii) a sequence encoding a Thosea asigna virus 2A (T2A) peptide that is present between the first coding sequence and the second coding sequence,
wherein the first and second polypeptides together specifically bind to one or more mammalian VEGF proteins,
wherein the mammal has an inner ear disorder and the inner ear disorder is vestibular schwannoma or neurofibromatosis type II, and
wherein the delivery of the AAV vector results in a reduction in VEGF activity in the inner ear of the mammal.
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