Methods of predicting ancestral virus sequences and uses thereof
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.
1. An adeno-associated virus (AAV) capsid polypeptide having the amino acid sequence shown in SEQ ID NO: 3.
2. The AAV capsid polypeptide of claim 1 , wherein the AAV capsid polypeptide or a virus particle comprising the AAV capsid polypeptide:
exhibits a lower seroprevalence than does an AAV2 capsid polypeptide or a virus particle comprising an AAV2 capsid polypeptide, and 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 AAV8 capsid polypeptide or a virus particle comprising an AAV8 capsid polypeptide; and/or
is neutralized to a lesser extent by human serum than is an AAV2 capsid polypeptide or a virus particle comprising an AAV2 capsid polypeptide, and 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 as is an AAV8 capsid polypeptide or a virus particle comprising an AAV8 capsid polypeptide.
3. The AAV capsid polypeptide of claim 1 , wherein the AAV capsid polypeptide is purified.
4. The AAV capsid polypeptide of claim 1 encoded by the nucleic acid sequence shown in SEQ ID NO: 4.
5. A nucleic acid molecule encoding an adeno-associated virus (AAV) capsid polypeptide having the nucleic acid sequence shown in SEQ ID NO: 4.
6. A vector comprising the nucleic acid molecule of claim 5 .
7. An isolated host cell comprising the vector of claim 6 .
8. A purified virus particle comprising the AAV capsid polypeptide of claim 1 .
9. The purified virus particle of claim 8 , further comprising a transgene.