ASGT Annual Meeting

Program

ASGT 6th Annual Meeting
June 4-8, 2003, Washington, D.C.
Jointly sponsored by Baylor College of Medicine, Houston, Texas

Program Schedule

Wednesday, June 4
Noon - 8:00 pm	Attendee Registration Open
3:00 pm	Clinical Gene Transfer Comprehensive Review Course Ends
2:00 pm – 3:45 pm	Programs of Excellence in Gene Therapy Wilson Co-Chairs Sonia Skarlatos, PhD Ronald G. Crystal, MD Speakers Sonia Skarlatos, PhD - Overview on the NHLBI Programs of Excellence in Gene Therapy Williams Goins, PhD - HSV Gene Vector Targeting Ronald G. Crystal, MD - Genetic Strategies for Antibacterial Vaccines Dusty Miller, PhD - Gene Therapy for Cystic Fibrosis Using AAV Vectors Mark Kay, MD, PhD - Mechanisms of AAV Transduction In Vivo
	The Genetic Modification Clinical Research Information System (GeMCRIS) Washington Room 4 The Genetic Modification Clinical Research Information System (GeMCRIS), will facilitate the evaluation and analysis of human gene transfer clinical research data. This database will enable users with different levels of expertise and interest to search for any number of specific variables, analyze aggregate data, and identify emerging trends in gene transfer research. The goal is to develop an electronic resource that both the general public and the scientific community will be able to easily access and use. GeMCRIS, in collaboration with FDA, will be an electronic resource available to both the general public and the scientific community. GeMCRIS will enhance the development of human gene transfer clinical trials while optimizing patient safety, identifying critical information gaps, facilitating the sharing of research strategies.
4:00 pm – 5:30 pm	Education Session I
	ES 100 - Retrovirus Vectors Cotillion North This session will discuss the use of oncoretroviruses and lentiviruses as vectors for gene therapy. Speakers will describe the biology and life cycle of oncoretroviruses, review the "state-of-the-art" of oncoretrovirus-based gene transfer technology, and discuss the potential for insertional mutagenesis. The biology and life cycle of lentiviruses will be described, and the recent development of performance- and safety-enhanced lentiviral vector systems containing genetic control elements that protect against chromosomal position effects and vector-mediated activation of endogenous genes. Speakers will address aspects related to the translation of lentivirus-based gene transfer technology to the clinic, covering production and safety issues as well as the "how to's" of the National Institutes of Health Recombinant DNA Advisory Committee's and the Food and Drug Administration's review/approval processes. Chair Robert G. Hawley, PhD Speakers Christopher Baum, MD - An Introduction into Retroviral Vectors Robert G. Hawley, PhD - ABCs of Lentiviral Vectors Boro Dropulic, PhD - Development of Lentiviral Vectors for the Clinic
	ES101 - AAV Vectors Cotillion South Adeno-associated virus (AAV) is emerging as one of the most promising viral vector systems for gene delivery. This workshop will present the basic biology of the AAV and review its potential in gene therapy. The session will begin with a talk that outlines the life-cycle of AAV, the role of viral and cellular proteins in replication and integration, and reviews ways of producing recombinant AAV vectors. There are multiple serotypes of AAV and these may have different uses as vectors. There will be discussion on the differences between the AAV serotypes in terms of their biology and applications for gene delivery. The session will end with an analysis of the pathways of AAV transduction and the fate of the viral genome. In addition to reviewing the biology of AAV, this session will present exciting recent developments in the uses of AAV for gene therapy. Chair Matthew Weitzman, PhD Speaker Matthew Weitzman, PhD - AAV: The Virus & The Vector John A. Chiorini, PhD - Biology of AAV Serotypes Joseph E. Rabinowitz, PhD - What Can the Crystal Structure of AAV Tell Us: Implication for Altering Tropism
	ES102 - Adenovirus Vectors Virginia The goal of this educational session is to provide an overview of adenovirus vectors and their application to gene therapy studies. Topics will include a review of adenovirus biology, a summary of the different classes of adenovirus vectors (E1-deleted, multiply-deleted, and fully-deleted vectors), and methods for their construction. In addition, there will be discussion on both the advantages and disadvantages of each vector class, highlighting relevant examples from pre-clinical and clinical studies. Other specific topics will include vector replication and delivery, and modifying the virus-cell interaction through vector retargeting. Chair Estuardo Aguilar-Cordova, PhD Speakers Estuardo Aguilar-Cordova, PhD - Adenoviral Vector Overview Susan C. Stevenson, PhD - Strategies for the Development of Targeted Adenoviral Vectors David H. Kirn, MD - Replication-selective Oncolytic Virotherapy for Cancer
	ES103 - Non-Viral Vectors Washington Room 2 The goal of this educational session is to provide an overview of the vector platform and their potential application to gene therapy studies. Topics will include a review of three non-viral vector systems (chemical and physical) and the considerations for their assembly and delivery. The relative advantages and disadvantages of the different systems with reference to examples from preclinical and clinical studies will be highlighted. Other topics that will be discussed include the toxicity that may be associated with administration of these vectors, and other challenges that need to be addressed before further evaluation in clinical studies can be contemplated. Chair Seng H. Cheng, PhD Speakers Jean-Paul Behr, PhD - In Vivo Gene Delivery Using PEI: An Update Richard Heller, PhD - Gene Transfer Using In Vivo Electroporation Dexi Liu, PhD - Hydrodynamic Gene Transfer and Functional Genomics
	ES104 - HSV and Large DNA Virus Vectors Wilson Vectors derived from DNA viruses, including Herpes Virus Type 1 and Herpes samiria, as well as vaccinia (pox), have a very large transgene capacity (100 - 300 kb) and can be designed as replicating episomes or integrating elements into the host cell genome. This session will cover background on these viruses and their use as vectors. Speakers will review Herpes simplex type 1 recombinant, amplicon and hybrid vectors in cancer therapy, and gene delivery to the nervous system. Pox vectors, including replication-selective, oncolytic poxvirus will be discussed along with high capacity episomal vectors based on the gamma herpes viruses, Epstein-Barr virus and Herpesvirus saimiri. Chair Miguel Sena Esteves, PhD Speakers Miguel Sena Esteves, PhD - HSV-1 Vectors: From Cold Sores to Genome Research Tools David L. Bartlett, MD - Vaccinia as a Vector for Gene Delivery Robert White, D. Phil - Gammaherpesviruses: Persistent High-Capacity Gene Delivery Vectors
	ES105 - Transgene Immunology Maryland Gene therapy often involves the delivery of genes encoding proteins that may be recognized as foreign to the host. This session will cover the basic biology of the immune system as it relates to gene therapy. An overview of the types of immune responses that might be generated against transgene-encoded proteins and transgene-expressing cells will be presented. The role of the immune system in responding directly to vector particles will also be discussed. Finally, methods for manipulating the immune system in ways that may improve gene delivery and prevent responses against novel therapeutic proteins will be reviewed. Chair Katherine A. High, MD Speakers Katherine A. High, MD - Transgene Immunology Overview Maria Grazia Roncarolo, MD - Modulation of Immune Responses to Transgenes Carl H. June, MD - Immunogenicity in Gene Therapy: Barriers and Solutions
	ES106 - NIH Grantsmanship Washington Room 4 The goal of this session is to acquaint participants with the grant review and funding process at the NIH. Participants will get advice on what contributes to a successful grant application from NIH staff. Staff will also provide information on funding opportunities in gene therapy as well as those available to support training. There will be an opportunity for questions during the panel discussion and NIH staff will be available for individual questions. This session will be aimed at new investigators but should be informative for any investigator planning to submit an NIH grant application. Chair Catherine McKeon, PhD Speakers Catherine McKeon, PhD - Understanding the NIH Review Process Terry R. Bishop, PhD - Training and Career Development Opportunities from the NIH Brendan Lee, MD, PhD - NIH Review: The Study Section Member's Perspective
5:30 pm - 6:45 pm	Dinner Break
6:45 pm – 8:15 pm	Education Session II
	ES110 - Retrovirus Vectors Cotillion North See description for Session 100 Chair Robert G. Hawley, PhD Speakers Christopher Baum, MD - An Introduction into Retroviral Vectors Robert G. Hawley, PhD - ABCs of Lentiviral Vectors Boro Dropulic, PhD - Development of Lentiviral Vectors for the Clinic
	ES111 - AAV Vectors Cotillion South See description for Session 101 Chair Matthew Weitzman, PhD Speaker Matthew Weitzman, PhD - AAV: The Virus & The Vector John A. Chiorini, PhD - Biology of AAV Serotypes Joseph E. Rabinowitz, PhD - What Can the Crystal Structure of AAV Tell Us: Implication for Altering Tropism
	ES112 - Adenovirus Vectors Virginia See description for Session 102 Chair Estuardo Aguilar-Cordova, PhD Speakers Estuardo Aguilar-Cordova, PhD - Adenoviral Vector Overview Susan C. Stevenson, PhD - Strategies for the Development of Targeted Adenoviral Vectors David H. Kirn, MD - Replication-Selective Oncolytic Virotherapy for Cancer
	ES113 - Non-Viral Vectors Washington Room 2 See description for Session 103 Chair Seng H. Cheng, PhD Speakers Jean-Paul Behr, PhD - In Vivo Gene Delivery Using PEI: An Update Richard Heller, PhD - Gene Transfer Using In Vivo Electroporation Dexi Liu, PhD - Hydrodynamic Gene Transfer and Functional Genomics
	ES114 - Replication-Competent Viral Vectors Wilson Chair Frank McCormick, PhD Speakers Frank McCormick, PhD - A Replication Compentent Adenovirus for Treating Human Cancer David T. Curiel, MD, PhD - Advanced Generation CRAd with Augmented Infectivity John C. Bell, PhD - The Development of Replicating Oncolytic Viruses for Cancer Therapy
	ES115 - Expression Cassette Design Maryland Room Essentially all gene therapy applications require functional expression of a transferred gene. This education session will focus on the design of gene expression cassettes for this purpose. There will be an overview of the basic components required to generate a functional gene expression cassette, as well as methods for reducing the effects of flanking chromatin on expression of integrating gene transfer vectors. This will be followed by a review of the various methods for optimizing expression from gene transfer vectors. The session will conclude with a review of the various methods for regulating the level of gene expression from engineered expression cassettes. Chair David W. Emery, PhD Speakers David W. Emery, PhD - Basic Expression Cassettes and Reducing Position Effects Punam Malik, MD - Optimizing Expression from Gene Transfer Vectors Victor Rivera, PhD - Regulated Gene Expression
	ES116 - FDA/OBA Regulations Washington Room 6 The session will provide a general overview of regulatory issues and procedures required for the conduct of clinical gene therapy trials. The session is geared for individuals who are considering entering the clinical arena and have not attended the Clinical Review Course. Specific topics to be discussed are current regulations governing gene therapy, applying for an IND to the FDA, RAC submission and oversight, and trial monitoring, requirements and compliance. Co-Chairs Kenneth Cornetta, MD Stephanie Simek, PhD Speakers Maritza C. McIntyre, PhD - Product Development Beyond Phase I Mercedes Serabian, MS, DABT - Preclinical Considerations Beyond Phase I: CBER Perspective
	ES117 - Gene Transfer for Cancer Therapy Washington Room 4 Cancer is fast becoming the leading cause of death in the United States, and is an exceptionally suitable target for gene therapy development. A multitude of scientific strategies have been exploited in the area of cancer gene therapy, which remains to be the one with the most clinical translational studies. The session on cancer gene therapy is intended to provide a broad-based overview of how three different scientific approaches have been developed to achieve tumor rejection in a variety of animal models of cancer. These strategies have also been tested in early to late phase clinical trials. Chair Savio L.C. Woo, PhD Speakers Savio L.C. Woo, PhD - Gene Transfer for Cancer Therapy Overview Richard J. Whitley, MD - To be announced Richard Cristiano, PhD - Tumor Suppressor Gene Therapy
8:15 pm - 8:30 pm	Break
8:30 pm – 10:00 pm	Education Session III
	ES120 - Hematopoietic Cell Gene Transfer Cotillion North This educational session will review basic concepts, recent advances and current issues in the generation of genetically modified hematopoietic stem and progenitor cells. The following concepts or topics will be addressed: stem cell sources, hierarchy, and plasticity; stem cell assays; human and non-human primate CD34+ cell transduction; regulation of transgene expression in the hematopoietic tissue; and insertional oncogenesis. Chair Michel Sadelain, MD PhD Speakers Craig Jordan, PhD - Marrow-Derived Stem Cells as Targets for Gene Therapy John Tisdale, MD - Requirements for Successful Hematopoietic Stem Cell Gene Transfer Michel Sadelain, MD PhD - Future Trends in Hematopoietic Stem Cell Gene Therapy
	ES121 - Central Nervous System Gene Transfer Cotillion South This session will discuss how the genetic modification of the brain through gene therapy approaches is applied to the study of brain structure and function, as well as to the development of novel treatments for degenerative diseases of the brain, such as Parkinson's disease and brain tumors. The session will explore advantages and limitations of individual viral vector systems (e.g., AAV, HSV-1, adenovirus, lentivirus) used to genetically modify brain cells, and how to select a given viral vector to best address scientific question being asked. The session will also discuss the interactions of viral vectors with the brain immune system, and what this means in terms of defining the limits of neurological gene therapy, and how these studies help us understand the brain's immune system. Participants will gain access to the theoretical challenges and recent practical advances in the genetic modification of the brain. Chair Pedro Lowenstein, MD, PhD Speakers Pedro Lowenstein, MD, PhD - The Boundaries of Neurological Gene Therapy: Viral Vectors and the Brain Immune System Krys Bankiewicz, MD, PhD - AAV-AADC Gene Transfer for Parkinson's Disease Howard J. Federoff, MD, PhD - HSV-1 Vectors as Tools for Behavioral Analysis
	ES122 - Muscle Gene Transfer Virginia Room Skeletal muscle is an important target for gene transfer due to the large number of inherited muscle diseases combined with the ability of muscle tissue to secrete proteins into the circulatory system. Genetic muscle diseases, such as the muscular dystrophies, will likely require efficient methods of gene transfer that can target a large percentage of the body muscle mass. In contrast, diseases such as hemophilia might be treated by delivery of genes to a small number of muscle fibers if efficient expression and secretion of the gene product can be obtained. This session will review viral, plasmid, and cellular methods that are being developed for gene transfer to muscle. Chair Jeffrey Chamberlain, PhD Speaker Jeffrey Chamberlain, PhD - Gene Transfer to Muscle Using Viral Vectors Hansell Stedman, MD - The Problem of Systemic Vector Delivery
	ES123 - Adult and Embryonic Stem Cells Maryland Room This session will focus on a description of stem cells sources from adult, fetal, and embryonic tissue. The basic characteristics, properties, and activities of these different stem cell populations will be discussed. Also detailed will be the differentiate properties of these stem cell populations and their function in both in vitro and in vivo models. The session will also include an update on the potential use of these cells for therapeutic application, and the progress toward reaching this goal. Chair Jane S. Lebkowski, PhD Speakers Jane S. Lebkowski, PhD - Adult and Embryonic Stem Cell Overview Mickie Bhatia, PhD - Differentiation Potential and Utility of Adult Versus Embryonic Stem Cells