Abstract: Disclosed are genetic expression cassettes, and vector comprising them useful for the delivery of nucleic acid segments encoding selected therapeutic constructs (including for example, peptides, polypeptides, ribozymes, and catalytic RN molecules), to selected cells and tissues of vertebrate animals. The disclosed genetic constructs are useful in the development of gene therapy vectors, including for example, viral vectors such as HSV, retroviral, lentiviral, AV, and rAAV vectors. The expression cassettes disclosed herein provide new tools in the field of gene therapy, and for the treatment of mammalian, and in particular, human diseases, disorders, and dysfunctions. The disclosed compositions may be utilized in a variety of investigative, diagnostic and therapeutic regimens, including the prevention and treatment of a variety of human diseases.