FINAL PROGRAM - American Society of Gene & Cell Therapy

38American Society of Gene & Cell TherapyProgram ScheduleWednesday, May 19 thDavid W. Russell, MD, PhDAAV-Mediated Gene TargetingAAV vectors efficiently recombine with homologous chromosomal sequences in mammalian cells. Up to 1% of the entire cell population exposed to vector particlesundergoes gene targeting under optimal conditions. Insertions, deletions and substitutions can all be introduced at precise chromosomal locations with high fidelity. Thetechnique works well in many cell types, including transformed cell lines, stem cells, and even in vivo in murine hepatocytes. Importantly, the gene targeting occurswithout genotoxicity and endonucleases are not required to obtain high targeting frequencies.Education Session 1325:30 pm - 7:00 pmRoom: Thurgood Marshall WTopical Review: Gene Delivery to the HeartHeart disease is one of the leading causes of morbidity and mortality worldwide. While molecular causes are known for many heart diseases, it requires effective heartgene delivery methods to translate these findings into therapy. Because of the dynamic nature of the heart physiology and the unique anatomic location, cardiac genetransfer has been a great challenge. Significant progress has been made over the last few years. In this session, a historical overview of heart gene transfer will be provided.Considering the importance of the large animal model in translational medicine, special emphasis will be given to cardiac gene delivery in the canine and porcinemodels.ChairDongsheng Duan, PhDSpeakersDongsheng Duan, PhDOverview of Heart Gene Transfer in MiceEfficient cardiac gene transfer holds great promise in treating heart diseases, a major health threat worldwide. Over the last decades, tremendous progresses have beenmade in delivering the marker and/or therapeutic genes to the mouse heart. This presentation will provide a historic review of the literature and an update of the currentdevelopments.Roger J. Hajjar, MDGene Therapy for Heart Failure: New Targets and New VectorsDespite the proliferation of therapies, congestive heart failure remains a progressive disease where a desperate need for innovative rather than incremental therapies toreverse the course of ventricular dysfunction. Recent advances in understanding the molecular basis of myocardial dysfunction, together with the evolution of increasinglyefficient gene transfer technology; have placed heart failure within reach of gene-based therapies. One of the key abnormalities in both human and experimental HF isa defect in sarcoplasmic reticulum (SR) function, which is responsible for abnormal intracellular Ca2+ handling. Restoring SERCA2a levels has been shown to improvefunction, metabolism and/or survival in a number of experimental models of heart failure. Over the last ten years we have undertaken a program of targeting importantcalcium cycling proteins in experimental models of heart by somatic gene transfer. This has led to the completion of a first-in-man phase 1 clinical trial of gene therapy forheart failure using adeno-associated vector (AAV) type 1 carrying SERCA2a. In this Phase I trial, there was evidence of clinically meaningful improvements in functionalstatus and/or cardiac function which were observed in the majority of Neutralizing antibody negative patients at various time points. The safety profile of AAV genetherapy along with the positive biological signals obtained from this phase 1 trial has led to the recent completion of a phase 2 trial of AAV1.SERCA2a in NYHA class III/IV patients.Charles R. Bridges, MD, ScDMethods for Cardiac Gene DeliveryThis presentation will review the available methods of cardiac vector mediated gene delivery including those in use in current clinical trials. Methods considered will includeintracoronary injection, intramuscular injection, pressurized coronary venous retroinfusion, and cardiopulmonary bypass-mediated techniques. The relative strengths andweaknesses of these delivery methods will be discussed with reference to efficiency of transfection, cardiac versus collateral organ specificity and relative propensity toinduce a T-cell mediated immune response.EXHIBITOR PROSPECTUSfinal program