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In particular, the invention provides AAV-based genetic constructs encoding one or more mammalian therapeutic proteins, polypeptides, peptides, antisense oligonucleotides, and ribozymes, as well as variants, and/or active fragments thereof, f~r use in the treatment and prophyla~is of a variety of conditions and mammalian diseases and disorders.

Current AAV2 targeting strategies involve inserting DIVA sequences that code for specific receptor ligands within the capsid open reading frame of the p I1~145 plasmid.

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Disclosed are improved VP2-modified recombinant adeno-associated viral (r AAV) vectors, expression systems, and r AAV virions that are fully virulent, yet lack functional VP2 protein expression. Methods are provided for preparing and using these modified r AAV-based vector constructs in a variety of viral-based gene therapies, and in particular, in the treatment, amelioration, and/or prevention of human diseases.1.2 DESCRIPTION OF RELATED ARTMajor advances in the field of gene therapy have been achieved by using viruses to deliver therapeutic genetic material.