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 at least 95% sequence identity to the amino acid sequence shown in SEQ ID NO: 23.
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 than 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 , wherein the polypeptide has at least 99% sequence identity to the amino acid sequence shown in SEQ ID NO: 23.
5. The AAV capsid polypeptide of claim 1 , wherein the polypeptide has 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 23.
6. A virus particle comprising the AAV capsid polypeptide of claim 1 .
7. The virus particle of claim 6 , further comprising a transgene.