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Discrete nor ca sexl chat

The lack or substantial absence of functional VP1 protein may be the result of at least a first mutation in the capsid gene sequence region that comprises the VP1 start codon, or alternatively in the VP1 start codon itself.An exemplary vector described herein is p IM45-VP2,3.Exemplary such vectors provided herein are p IM45-VP1, p IM45-VP2, or p IM45-VP3, which produce substantially a single VP1, VP2, or VP3 protein, respectively.Another embodiment of the invention is an expression vector that expresses: (a) r AAV capsid proteins VP1 and VP2 in the absence of substantial amounts of VP3 protein;(b) r AAV capsid proteins VP1 and VP3 in the absence of substantial amounts of protein; or (c) r AAV capsid proteins VP2 and VP3 in the absence of substantial amounts of VP1 protein.

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Such plasmids can be complemented with plasmids that express the remaining 2 capsid proteins (p IM45-VP2,3, p IM45-VP1,3, and p IM45-VP1,2, respectively) in order to produce viable recombinant AAV2 vectors.

In a third embodiment, the invention concerns r AAV vectors that comprise a nucleic acid segment modified to express functional VP2 and VP3 capsid proteins substantially in the absence of functional VP1 protein.

Although such vector cannot produce an infectious virion in the absence of exogenous VP1 protein, if a second helper vector that encodes a functional VP1 protein is employed to coinfect cells with this vector, infectious virions can be obtained.

Also disclosed are pharmaceutical compositions, virus particles, host cells, and pharmaceutical formulations that comprise these modified vectors useful in the expression of therapeutic proteins, polypeptides, peptides, antisense oligonucleotides and/or ribozymes in the cells and tissues of selected mammals, including, for example, human tissues and host cells. I~I~CI~GIIOUND OF THE INVENTIONThe present application claims priority to l Tnited States Provisional Application Serial No. The adeno-associated virus (AAV) has attracted considerable attention as a highly effective viral vector for gene therapy due to its low immunogenicity and ability to effectively transduce non-dividing cells.

The invention provides VP2-modified recombinant adeno-associated virus (r AAV) vectors that, while deleted for VP2, are still fully virulent.


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