The goals of this project/core are: 1) to develop a convenient , reliable and generally applicable strategy to monitor in vivo the expression of any vector encoded transgene; and 2) to supply all PPG investigators with well-characterized preparations of retroviral, lentiviral and adenoviral gene therapy vectors tailored to their individual requirements. The profile of therapeutic transgene expression is a key determinant of the outcome in any in vivo gene therapy study, but this information is usually not available. The overall hypothesis for the current project is that the expression of the therapeutic transgene can be non-invasively monitored in vivo by measuring the concentration in body fluids of a soluble, non- immunogenic marker polypeptide concordantly expressed from the same vector construct.
The Specific Aims are: 1) To precisely define the concordance between the rates of synthesis of vector encoded polypeptides whose expression is linked through an internal ribosome entry site (IRES); 2) To define the in vivo gene expression profiles and concordance over time between body fluid concentrations of soluble marker peptides expressed from the bicistronic lentiviral and adenoviral vectors of preparations of retroviral, lentiviral or adenoviral vectors incorporating the optional feature of concordantly expressed beta-hCG marker polypeptide to support their preclinical studies in immunocompetent rats, dogs and pigs.
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