651 Construction and Characterization of Cardiac Specific and Stress Inducible Promoters Molecular Therapy Volume 17, Supplement 1, May 2009 Copyright © The American Society of Gene Therapy S248 GENE[.]
GENE REGULATION: ORGANOTROPIC APPROACHES - HEART, MUSCLE, LIVER, NEURO, BLOOD Gene Regulation: Organotropic Approaches Heart, Muscle, Liver, Neuro, Blood 649 Non Viral Delivery of Stromal Derived Cell Factor -1 Gene Improves Cardiac Function in Heart Failure Srividya Sundararaman, Joseph Pastore, Matthew Kiedrowski, Farhad Forudi, Rahul Aras, Marc S Penn Stem Cell and Regenerative Biology, Cleveland Clinic, Cleveland, OH; Applied Biomedical Engineering, Cleveland State University, Cleveland, OH Stromal Derived Cell Factor -1 (SDF- 1) is a chemokine that is transiently expressed following a myocardial infarction (MI) We have previously demonstrated using a cell based gene therapy approach that the reestablishment of SDF-1 expression weeks after MI improves cardiac function We believe that a similar improvement can be observed when SDF-1 is delivered via a non-viral plasmid that can be translated to a clinical setting We optimized plasmid delivery via two CMV driven plasmids, one with transcriptional enhancers (pKCb) and without (p3Cb) and determined plasmid expression and functional improvement in both Methods and Results: The expression profile, in vivo, was characterized by quantifying the chemiluminescence emitted when the gene of interest encoded by the plasmid was Luciferase The plasmid with transcriptional enhancers, pKCb showed a significantly greater magnitude of expression but did not change the length of expression over time, as compared to p3Cb Using luciferase signal, we found that 100 ug per injection yielded maximal activity Using this dose and injection sites in the border zone, we injected the same plasmid backbone now encoding hSDF-1 one month after MI, to test for functional benefit Left ventricular function was assessed by measuring Fractional Shortening % (FS%) via echocardiography at baseline, weeks, weeks and weeks post injection Four weeks after plasmid injection (8 w after MI) there was a 36.3% decline in FS% in saline control animals (n=10) In contrast, we observed a significant 3.0% and 15.4% increase in FS% during the same w period with p3Cb-SDF1 (n=10) and pKCb-SDF-1 (n=9), respectively,(p