Includes bibliographical references (p. 147-188).It is the objective of this project to produce gene therapy vectors that are active and/or significantly up-regulated due to specific physiological conditions. The significance of such constructs is that it imparts a greater degree of control in the implementation of gene therapy. In general, it is desirable for a gene therapy vector to be active only when and where it is needed. The majority of gene therapy research to date has focused primarily on obtaining expression levels high enough to elicit a therapeutic response, as well as, distributing the vector to enough tissues to provide a corrective effect to the disorder being addressed. However, simply having a gene adequately delivered to enough cells to treat disease and having the gene product be produced in sufficient amounts to have a therapeutic effect cannot be the end of the story. Not unlike genes found naturally in the body, artificially delivered genes also need to be regulated. The construction of such vectors could prove useful for the treatment of disorders; such as Coronary Artery Disease (CAD) or even Cardiomyopathy, that occur in a specific tissue type or that are associated with an abnormal physiological state, such as hypoxia. Our vector constructs are a small step towards this ultimate goal. In this study, we present data on DNA vectors that were designed, constructed and evaluated in vitro and in vivo; both qualitatively and quantitatively. We report success in the creation of vectors/plasmids that are primarily cardiac tissue specific (pMHCI, pMHCII), vectors that are regulated by cellular oxygen levels (pHAL, pHAM), and even some success in combining the two (pHMHC).by David Rowe Wood.Ph.D.