FINAL PROGRAM - American Society of Gene & Cell Therapy

13 th AnnUAL MEETing | Washington, DC USA May 19-22, 2010 69Program ScheduleYiping Yang, MD, PhDInnate Immunity in AAV-mediated Gene TherapyRecombinant adeno-associated viruses (AAVs) have been used widely for in vivo gene therapy. However, adaptive immune responses to AAV have posed a significanthurdle in clinical application of AAV vectors. Recent advances have suggested a crucial role for innate immunity in shaping adaptive immune responses. Here I will discusshow AAV activates the innate immune system and the potential implications for improving the outcome of AAV-mediated gene therapy.David B. Weiner, PhDHigh Immune Potency of Highly Optimized EP DNA Vaccines in Animal Models and HumansDNA vaccines are an important emerging vaccine technology, however the immune responses induced by past generations of DNA vaccines were poor in larger animalsincluding nonhuman primates and importantly humans. We have recently utilized a combination of technologies for plasmid optimization, combined with enhanced EPdelivery to dramatically improve the immune potency of this platform. These new EP systems also offer improved tolerability and effectiveness. We will present data inanimal models and humans illustrating immune aspects of the technology for application to human infectious diseases.Michael T. Lotze, MDMicroRNAs in Immune Regulation-Opportunities for Cancer Gene TherapyInitially considered as means to regulate tissue differentiation and disordered in cancer, miRNAs [miR] have now been identified that are induced in response to hypoxia,oncogenic signaling, pathogens and tissue damage or injury. Each miR can regulate the translation of up to 100 separate mRNAs. Means to either express or knockdownmiRNA expression [so-called antagomiRs] have been operationalized in murine models and represent exciting novel targets for modifying immunity.Scientific Symposium 4048:30 am - 10:30 amRoom: Wilson ABCMicroRNA and siRNA Roles in Disease Progression and Development of Novel Therapeutic TargetsChairMaria G. Castro, PhDSpeakersAnna M. Krichevsky, PhDMicroRNAs as Targets for Glioma TherapyMicroRNA (miRNA) is a class of small RNA molecules involved in the regulation of expression of at least 30% of human genes and, therefore, it controls all principalcellular processes, including cell division and cell death. In my talk, I will describe our approach to reveal key miRNA regulators in human diseases and focus on miRNAfunctions in the development of human brain tumors. Our recent work presents proof-of-principles that specific inhibition of a single oncogenic miRNA could provide a noveltherapeutic approach for physiological modulation of multiple proteins whose expression and activity is de-regulated in cancer. It also suggests a diagnostic potential forthis novel class of molecules.M. Maral Mouradian, MDMicroRNAs in Parkinson’s Disease and Other Neurodegenerative Disordersalpha-Synuclein is a key protein that accumulates in the brains of patients with Parkinson’s disease and related neurodegenerative disorders. Evidence from clinical geneticstudies, animal models and cell biologic experiments indicate that elevated levels of this protein are toxic. This presentation will discuss down-regulation of alpha-synucleinexpression by microRNA leading to neuroprotection.Sean E. Lawler, PhDMicroRNA Alterations and Functions in GlioblastomaMicroRNAs have recently emerged as important regulators of gene expression with potential therapeutic applications in many human diseases. We have identified extensivealterations in microRNA expression in the malignant brain tumor glioblastoma multiforme. We have shown that altered microRNAs play roles in proliferation, stemcell-like behavior, and glioma cell migration. This talk will focus on the underlying mechanisms of microRNA action in glioblastoma, and their therapeutic potential.Saturday, May 22 nd