Methods and compositions for modifying assembly-activating protein (AAP)-dependence of viruses
US-11034732-B2 · Jun 15, 2021 · US
US2021017235A1 · US · A1
| Field | Value |
|---|---|
| Publication number | US-2021017235-A1 |
| Application number | US-202016989454-A |
| Country | US |
| Kind code | A1 |
| Filing date | Aug 10, 2020 |
| Priority date | Jul 30, 2015 |
| Publication date | Jan 21, 2021 |
| Grant date | — |
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Methods are described for predicting ancestral sequences for viruses or portions thereof. Also described are predicted ancestral sequences for adeno-associated virus (AAV) capsid polypeptides. The disclosure also provides methods of gene transfer and methods of vaccinating subjects by administering a target antigen operably linked to the AAV capsid polypeptides.
Opening claim text (preview).
What is claimed is: 1 . An adeno-associated virus (AAV) capsid polypeptide having the amino acid sequence shown in SEQ ID NO: 42. 2 . The AAV capsid polypeptide of claim 1 , wherein the AAV capsid polypeptide or a virus particle comprising the AAV capsid polypeptide exhibits about the same or a lower seroprevalence than does an AAV9 capsid polypeptide or a virus particle comprising an AAV9 capsid polypeptide. 3 . The AAV capsid polypeptide of claim 1 , wherein the AAV capsid polypeptide or a virus particle comprising the AAV capsid polypeptide is neutralized to a similar or lesser extent by human serum than is an AAV9 capsid polypeptide or a virus particle comprising an AAV9 capsid polypeptide. 4 . The AAV capsid polypeptide of claim 1 , wherein the AAV capsid polypeptide is purified. 5 . The AAV capsid polypeptide of claim 1 encoded by the nucleic acid sequence shown in SEQ ID NO: 43. 6 . A nucleic acid molecule encoding an adeno-associated virus (AAV) capsid polypeptide having the nucleic acid sequence shown in SEQ ID NO: 43. 7 . A vector comprising the nucleic acid molecule of claim 6 . 8 . A host cell comprising the vector of claim 7 . 9 . A purified virus particle comprising the AAV capsid polypeptide of claim 1 . 10 . The purified virus particle of claim 9 , further comprising a transgene. 11 . A method of gene transfer and/or vaccination with a transgene, the method comprising administering the virus particle of claim 10 to a subject in need of gene transfer or vaccination, wherein the virus particle exhibits about the same or a lower seroprevalence than does an AAV9 virus particle. 12 . The method of claim 11 , wherein the virus particle is neutralized to the same or to a lesser extent by human serum than is an AAV9 virus particle. 13 . A method of vaccinating a subject, the method comprising administering a target antigen operably linked to the AAV capsid polypeptide of claim 1 to a subject in need of vaccination, wherein the AAV capsid polypeptide exhibits about the same or a lower seroprevalence than does an AAV9 capsid polypeptide. 14 . The method of claim 13 , wherein the AAV capsid polypeptide is neutralized to the same or to a lesser extent by human serum than is an AAV9 capsid polypeptide.
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