Program Schedule
(This program is subject to updates/changes.)
Room: 314/317
Chair: Luigi Naldini, MD, PhD
The purpose of this special session is to unite gene therapy researchers with vast research interests but a common goal of advancing the field of gene transfer research as a basic science and clinical entity. The ASGT Program Committee has selected research scientists from various countries throughout the globe, all of whom have exciting scientific programs and have offered to update the society members on recent accomplishments. All members are welcome to take advantage of this opportunity to learn what their colleagues are doing.
Speakers:
Sunyoung Kim, PhD
Development of Gene Medicines Using Naked DNA and Retroviral Vectors for Various Human Diseases
Zhaohui Peng, PhD
New Process of Gendicine for Treatment of Cancers in China
Yasufumi Kaneda, MD
Progress of Human Gene Therapy in Japan: Clinical Trials and Vector Development
Jean-Michel Heard, PhD
Gene Therapy for Degeneration in Lysosamal Storage
Gloria Gonzalez-Aseguinolaza, PhD
Gene Therapy for Viral Hepatitis
Luigi Naldini, MD, PhD
Targeting Gene Therapy Exploiting Cell Homing, Transcriptional, and Micro-RNA-Based Regulation
Deborah Gill, PhD
Improving the Persistence of Gene Expression for Chronic Lung Disease
Room: 318/320
Chair: Boro Dropulic, PhD
The success of gene transfer technologies will depend as much on manufacturing technology as safety and efficacy. More importantly, it is now clear manufacturing technology by itself can influence safety and efficacy. As a result, manufacturing technology needs to be addressed early in the development cycle. Yet significant challenges remain to assure sufficient product to support development and clinical programs while maintaining product quality. These challenges are further complicated because concepts of product purity and the analytical methods to evaluate purity are still evolving. In addition, any manufacturing process, regardless of product, must assure:
- Consistency of purity to desired specifications
- Consistent potency of the product
- Efficiency of the process
- Scalability of the process
- Compatibility with cGMP manufacturing guidelines
This session will focus on the rapid improvements in the manufacture of gene-transfer products: supercoiled plasmids, adenovirus, adeno-associated virus, lentivirus and cell therapies. The presentations will include reviews of the state-of-the-art for these transfer vectors as well as the important challenges that need to be addressed.
Speakers:
Anthony Green, PhD
Plasmids
Andy Lin, PhD
Meeting Product Development Challenges in Manufacturing Oncolytic Adenoviruses
J. Fraser Wright, PhD
Preparing AAV Vectors for Clinical Applications: Great Potential and Remaining Challenges
Isabelle Riviere, PhD
Retroviral Vector Production in the Academic Setting
Vladimir Slepushkin, MD, PhD
Manufacturing of Lentiviral Vectors for Clinical Trials
Bruce L. Levine, PhD
Manufacture of Lentivirus Transduced T Cells
Elizabeth Read, MD
Manufacturing Issues for G-CSF Mobilized Hematopoietic Progenitor Cells Transduced with Retroviral Vectors
Ray Harris, PhD
Production and Purification of a HSV-1 Based Gene Vector for Phase-1 Clinical Trial
This session is supported by VIRxSYS.
The biological properties of adeno-associated virus provided an attractive platform for the development of gene delivery vectors. The simplicity, lack of pathogenicity, and broad cell-type tropism of the archetypal AAV seryptype 2 allowed stable expression of exogenous genes in many different tissues. In order to expand the utility of the vectors, these basic properties have been built upon in recent years to discover and create a menagerie of new derivatives of recombinant AAV that overcome specific limitations in efficiency, tropism, transgene capacity, and production. In some cases, these represent fundamental alterations in the biology of the of the parent parvovirus. This session will include three presentations, providing an overview of the many different ways that the DNA genome, the capsid, and the producer cells have been engineered to meet the challenges of safe, successful, and economically feasible gene therapy.
Room: 321/323
Chair: Douglas M. McCarty, PhD
Speakers:
Sergei Zolotukhin, PhD
Current Approaches for a Large-Scale rAAV Production
Jeffrey S. Bartlett, PhD
Definition and Modification of AAV Vector Tropism
Douglas M. McCarty, PhD
AAV Vectors: Engineering the Virus
The purpose of the session is to present a view of what should be considered in a strategy for building an immunotherapy for cancer. The strategies that require consideration are dependent on product-specific issues that may affect choices from the bench to the bedside. This session will highlight the diversity of choices that can be applied towards successful strategies for various cancer immuno-therapy products. The session, we hope, will provide attendants with an overview of three different, valid endpoints and thus strategies to develop potentially valuable therapeutics for the clinic - with an emphasis on the importance of the immune system.
Room: 327/329
Chair: Estuardo Aguilar-Cordova, PhD
Speakers
Malcoom Brenner, MD, PhD
Can Cell-Based Genetic Immunotherapies for Cancer be Developed in an Academic Center
Paul H. Fischer, PhD
Building a Strategy for Transitional Medicine
Estuardo Aguilar-Cordova, PhD
Adenovirus Thymidine Kinase: In-situ Cytoxicity as an Approach to Systemic Immunotherapy
A successful gene therapy approach is ultimately one that improves the health of patients. The goal of this education session will be to present an overview of the clinical development process and discuss major issues which are confronted along the way. The session will present both an academic and industry perspective to drug development. An example of taking a project from the laboratory, through manufacturing and into clinical trials within academia will be presented. Challenges to clinical drug development in academia to be highlighted include the impact of regulatory concerns and early clinical development decisions on future drug development plans and industrial partnerships.
Clinical development issues faced by industry will be discussed including: When to take a drug into the clinic? Why drugs fail? What are the economic criteria for drug development in the pharmaceutical industry?
Room: 343/344
Chair: Laura K. Aguilar, MD, PhD
Speakers:
Stephen L. Eck, MD, PhD
Oncology Drug Development Issues: An Industry Perspective on Improving the Likelihood of Success
Leisha A. Emens, MD, PhD
Clinical Translated Research in Academia: From Concept to Delivery
Laura K. Aguilar, MD, PhD
Overview of Clinical Development Issues
The goal of this session is to acquaint participants with the NIH grant application, review and funding process. In particular, we will highlight the new electronic grant submission process. Participants will hear from program staff and a Study Section member on what contributes to a successful grant application. Program Staff will provide information on funding opportunities in gene therapy as well as new opportunities for funding for trainees.
Room: 345/346
Chair: Catherine McKeon, PhD
Speakers:
Catherine McKeon, PhD
A Grantwriter’s Guide to the NIH
Terry R. Bishop, PhD
Pathways to Independence
John F. Engelhardt, PhD
Writing Competitive Grants
The program will review the state-of-the-art in integrative gene transfer mediated by retroviral and lentiviral vectors into hematopoietic cells, highlighting both the current challenges regarding vector safety and the new opportunities opened up for gene therapy. Special emphasis will be given on the following topics: identification of cellular factors controlling the efficiency of transduction; how to assess the impact of integration on genome function and cell growth properties; exploiting integrating vectors as clonal markers to monitor stem cell activity in vivo; the unexpected consequences, both detrimental and beneficial, of insertional mutagenesis in the hematopoietic system; the new sophistication reached in gene transfer design that has allowed the delivery of complex expression cassettes with exquisite lineage-specific expression control, such as in the case of globin genes in erythroid lineages, combined with the expression of RNA interference and/or selectable markers. All the speakers will discuss how to translate basic concepts and scientific advances into the design and execution of new clinical trials.
Room: 337/338
Chair: Luigi Naldini, MD, PhD
Speakers:
Christof von Kalle, MD
Biological Effects of Retrovirus Vector Insertion
Michel Sadelain, MD PhD
Regulated Transgene Expression and RNA Interference in Hematopoietic Stem Cells
Luigi Naldini, MD, PhD
Safety and Efficacy of Lentiviral Gene Transfer
RNA interference is now recognized as a potent and important mechanism for post-transcriptional regulation of gene expression. There are two major arms of the RNAi pathway that are being exploited for gene therapy. The first is the small interfering RNA mechanism, which leads to small RNA directed message destruction. The other is the endogenous micro RNA pathway which is involved in broad based regulation gene expression via modulation of protein translation. This educational session will overview the mechanistic aspects of RNAi as well as provide experimental approaches for using RNAi in genetic therapies. Examples of applications of RNAi to viral and genetic diseases will be presented. The goal of this workshop is to provide a knowledge foundation of RNAi and provide a framework for investigators to use RNAi in gene therapy applications.
Room: 339/342
Chair: John J. Rossi, PhD
Speakers:
Scott Harper, PhD
Applying RNAi to Cells and Animals
Anton P. McCaffrey, PhD
The MicroRNA Pathway: A New Gene Therapy Target
John J. Rossi, PhD
The Nuts and Bolts of RNA Interference
Genomic integration of recombinant gene transfer vectors is a reliable strategy to maintain the presence and in some cases long-term expression of newly introduced genes in target cells and tissues. This Education Session will present molecular strategies and characteristics of integrating vectors as well as the consequences of vector integration. Viral vectors, which have long been used to achieve high efficiency gene integration, will be discussed, including new emerging viral vectors. More recently developed systems for achieving non-viral gene integration will also be discussed. Finally, the mutagenic consequences of vector integration, for which there has been considerable concern recently, will be addressed.
Room: 324/326
Chair: R. Scott McIvor, PhD
Speakers:
David W. Russell, MD, PhD
Viral Vector Intergration
R. Scott McIvor, PhD
Non-Viral Integration
Christopher Baum, MD
Mutagenesis by Retroviral Vector Insertion - Manifestation and Prevention
Adenovirus vectors are one of the most commonly used delivery vehicles in gene therapy applications. The goal of this educational session is to provide an overview of adenovirus vectors and their application to gene therapy studies. We will review adenovirus biology and discuss the various classes of adenovirus vector, including E1-deleted, multiply-deleted, and fully-deleted vectors, as well as conditionally replicating/oncolytic virus and adenovirus vectors based on non-human serotypes. In addition, we will summarize both the advantages and disadvantages of each vector class, highlighting relevant examples from pre-clinical and clinical studies. Other specific topics will include immunological responses to vector delivery and modifying the virus-cell interaction through vector retargeting.
Room: 321/323
Chair: Robin J. Parks, PhD
Speakers:
Eric Kremer
Adenovirus Entry and Trafficking
Andrea Amalfitano, DO, PhD
Immune System Interactions with Adenovirus Vectors
Robin J. Parks, PhD
Molecular Biology of Adenovirus Vectors
Over 80 different monogenic diseases are known to affect muscle function. Irreversible deterioration of this essential organ is also observed in autoimmune cancer and aging. Wasting of the skeletal muscles prevents movements and locomotion, while loss of integrity in the heart and the diagram compromises respiratory and cardiac functions. In front of such a complex and devastating picture, gene therapy appears to be a tall order, if not a desperate cause. Yet, significant progresses have been made over the past few years, up to a point where true benefit for heavily handicapped patients can now be foreseen. Efficient vectors for gene transfer into the muscle can be administered locally by intra-muscular or intra-myocardial injections, or regionally using vascular perfusion. These gene transfer technologies have permitted to demonstrate therapeutic effects in animal models of muscular dystrophies. The diverse aspects of translating these exciting progresses into clinical trials and effective treatments will be discussed.
Room: 327/329
Chair: Olivier Danos, PhD
Speakers:
Olivier Danos, PhD
Gene Therapy for Duchenne Muscular Dystrophy
Kathryn Wagner
Current Therapy of Muscular Dystrophy
Barry J. Byrne, MD, PhD
Gene Therapy for Muscular Dystrophy: Can We Make Enough Vectors?
This session will focus on providing basic guidance for the design of new expression cassettes for use in gene therapy. Although the content will be tailored to those individuals with little experience in constructing new vectors, we are broadening the subject matter to include novel platforms beyond traditional cDNA cassettes.
Room: 339/342
Chair: John T. Gray, PhD
Speakers:
John T. Gray, PhD
Squeezing it in: The Basics of cDNA Expression Cassettes and Making Them Fit into Small Capacity Vectors
Christopher Walsh, MD PhD
Spliceosome-Mediated Gene Correction
Dirk Grimm, PhD
Design of Expression Cassettes for the In Vivo Transcription of Short Hairpin RNAs
Immune responses to the transgene product or the gene transfer vector are major obstacles for treatment of genetic disease. On the other hand, enhancing immune responses could lead to efficacious genetic vaccines. This session provides an overview of immunology as it relates to gene transfer, explains mechanisms of immune tolerance and regulation that can lead to hypo-responsiveness to therapeutic gene products, and informs about strategies for development of gene-based vaccines.
Room: 343/344
Chair: Roland W. Herzog, PhD
Speakers:
Roland W. Herzog, PhD
Introduction to Immunology of Gene Transfer
Philip R. Johnson, MD
Immunology of Genetic Vaccines
John Iacomini, PhD
Preventing Immune Responses through Tolerance Induction
This session will describe the barriers to nonviral gene transfer and strategies used to circumvent them. In particular, access to the nucleus of nondividing cells has been a substantial impediment to efficient gene therapy. Newer polyplexes may bind to shuttle proteins or take advantage of compaction of DNA to overcome this difficulty and achieve efficient nuclear entry.
Room: 324/326
Chair: Pamela Davis, MD, PhD
Speakers
Pamela Davis, MD, PhD
Non-viral Vectors: Gaining Access
Kevin G. Rice, PhD
Delivery of DNA from the Needle to the Nucleus
Stephen Hart, PhD
The Development of Receptor-Targeted Nanocomplexes for Gene Therapy
This session illustrates how understanding the biology of viruses guides engineering of replicating vectors for use in cancer clinical trials. Three systems will be presented: a simple RNA virus (measles), a slightly more complex DNA virus (adeno), and a large DNA virus (herpes). Targeting principles applicable to viruses currently used in cancer clinical trials will be presented, and strategies for improving their therapeutic indexes discussed.
Room: 337/338
Chair: Roberto Cattaneo, PhD
Speakers:
Samuel D. Rabkin, PhD
Oncolytic Herpes Viruses
Andre Lieber, MD PhD
Challenges for Tumor Targeting with Adenoviruses Vectors
Roberto Cattaneo, PhD
Oncolytic Measles Viruses: The New Battlegrounds
One strategy to increase the safety and efficacy of gene therapy is to develop cell-targeting gene therapy vectors to deliver genes specifically into diseased cells while avoiding delivery into non-target tissues. This education session will present the key elements of vector targeting including ligand discovery, the role of ligand affinity, translation of ligands into viral vectors, ligand and vector structural compatibility, and vector-specific difficulties and successes. The session will also discuss the pharmacology of vector targeting including: the differing function of vector ligands in vitro and in vivo, the role of blood proteins in masking vector ligands and retargeting to unexpected receptors, the barriers to tissue penetration, and efforts to effectively evaluate vector targeting in preclinical animal models.
Room: 345/346
Chair: Michael A. Barry, PhD
Speakers
Michael A. Barry, PhD
Stephen J. Russell, MD, PhD
Engineering the Receptor Specificity of Enveloped Viruses
Andrew H. Baker, PhD
Targeting Adenoviruses and AAV
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