High-transduction-efficiency rAAV vectors, compositions, and methods of use
AssigneeUniversity of Florida Research Foundation, Inc.
InventorsArun Srivastava, George Vladimirovich Aslanidi, Kim M. Van Vliet, Mavis Agbandje-McKenna
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Abstract
The present invention provides AAV capsid proteins comprising modification of one or a combination of the surface-exposed lysine, serine, threonine and/or tyrosine residues in the VP3 region. Also provided are rAAV virions comprising the AAV capsid proteins of the present invention, as well as nucleic acid molecules and rAAV vectors encoding the AAV capsid proteins of the present invention. Advantageously, the rAAV vectors and virions of the present invention have improved efficiency in transduction of a variety of cells, tissues and organs of interest, when compared to wild-type rAAV vectors and virions.
Claims19
An isolated nucleic acid molecule that encodes a non-naturally occuring AAV capsid protein comprising one or more of the following modified residues:
- (a) a non-lysine amino acid residue at a position that corresponds to K258, K321, K459, K490, K507, K527, K572, K532, K544, K549, K556, K649, K655, K665, or K706 of the wild-type AAV2 capsid protein of SEQ ID NO:2;
- (b) a non-lysine amino acid residue at a position that corresponds to K530, K547, or K569 of the wild-type AAV8 capsid protein of SEQ ID NO:8;
- (c) a non-serine amino acid residue at a position that corresponds to S261, S264, S267, S276, S384, S458, S468, S492, S498, S578, S658, S662, S668, S707, or S721 of the wild-type AAV2 capsid protein of SEQ ID NO:2;
- and/or
- (d) a non-threonine amino acid residue at a position that corresponds to T251, T329, T330, T454, T455, T503, T550, T592, T581, T597, T491, T671, T659, T660, T701, T713, or T716 of the wild-type AAV2 capsid protein of SEQ ID NO:2.
Dependencies are inferred from the claim text.