Chimeric Vectors
First Claim
1. A chimeric virus vector comprising:
- (a) a chimeric adeno-associated virus (AAV) capsid comprising a selective amino acid insertion following amino acid position 264 in an AAV2 capsid subunit or a corresponding change in a capsid subunit from other AAV; and
(b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence;
wherein the nucleic acid is packaged within the chimeric AAV capsid.
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Accused Products
Abstract
The present invention is based, in part, on the discovery that parvovirus (including AAV) capsids can be engineered to incorporate small, selective regions from other parvoviruses that confer desirable properties. The inventors have discovered that in some cases as little as a single amino acid insertion or substitution from a first parvovirus (e.g., an AAV) into the capsid structure of another parvovirus (e.g., an AAV) to create a chimeric parvovirus is sufficient to confer one or more of the desirable properties of the first parvovirus to the resulting chimeric parvovirus and/or to confer a property that is not exhibited by the first parvovirus or is present to a lesser extent.
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Citations
51 Claims
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1. A chimeric virus vector comprising:
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(a) a chimeric adeno-associated virus (AAV) capsid comprising a selective amino acid insertion following amino acid position 264 in an AAV2 capsid subunit or a corresponding change in a capsid subunit from other AAV; and (b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence; wherein the nucleic acid is packaged within the chimeric AAV capsid. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51)
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20. A chimeric virus vector comprising:
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(a) a chimeric adeno-associated virus (AAV) capsid comprising; (i) a selective amino acid substitution of an alanine for glutamine at amino acid position 263 in an AAV2 capsid subunit; (ii) a selective amino acid insertion of a threonine following amino acid position 264 in the AAV2 capsid subunit; (b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence; wherein the nucleic acid is packaged within the chimeric AAV capsid.
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21. A chimeric virus vector comprising:
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(a) a chimeric adeno-associated virus (AAV) capsid comprising; (i) a selective amino acid substitution of an alanine for glutamine at amino acid position 263 in an AAV3b capsid subunit; (ii) a selective amino acid insertion of a threonine following amino acid position 264 in the AAV3b capsid subunit; (b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence; wherein the nucleic acid is packaged within the chimeric AAV capsid.
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22. A chimeric virus vector comprising:
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(a) a chimeric adeno-associated virus (AAV) capsid comprising a selective amino acid substitution at amino acid position 450 in an AAV2 capsid subunit or a corresponding change in a capsid subunit from other AAV; (b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence; wherein the nucleic acid is packaged within the chimeric AAV capsid. - View Dependent Claims (23)
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24. A chimeric virus vector comprising:
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(a) a chimeric adeno-associated virus (AAV) capsid comprising a selective amino acid substitution at amino acid position 457 in an AAV2 capsid subunit or a corresponding change in a capsid subunit from other AAV; (b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence; wherein the nucleic acid is packaged within the chimeric AAV capsid. - View Dependent Claims (25, 26)
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27. A chimeric virus vector comprising:
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(a) a chimeric adeno-associated virus (AAV) capsid comprising; (i) a selective amino acid insertion following amino acid position 264 in an AAV2 capsid subunit or a corresponding change in a capsid subunit from other AAV; (ii) a selective amino acid substitution at amino acid position 263 in the AAV2 capsid subunit or a corresponding change in the capsid subunit from other AAV; (iii) a selective amino acid substitution at amino acid position 705 in the AAV2 capsid subunit or a corresponding change in the capsid subunit from other AAV; (iv) a selective amino substitution at amino acid position 708 in the AAV2 capsid subunit or a corresponding change in the capsid subunit from other AAV; and (v) a selective amino substitution at amino acid position 716 in the AAV2 capsid subunit or a corresponding change in the capsid subunit from other AAV; and (b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence; wherein the nucleic acid is packaged within the chimeric AAV capsid. - View Dependent Claims (28)
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Specification