Session Types and their Definitions
| Wednesday,
June 5 |
| Noon
– 8:00 pm |
Attendee
Registration Open |
| 2:00
pm – 4:00 pm |
ASGT
Board Meeting (Sheraton) |
| 3:30
pm |
Review
Course Ends (Sheraton) |
| 4:00
pm – 5:30 pm |
8
Education Sessions |
| |
Education
Session ES100
Retrovirus Vectors
This session will
discuss the use of retroviruses and lentiviruses as vectors for gene therapy.
Speakers will describe the biology and life cycle of retroviruses, and review
the "state-of-the-art" of retrovirus-based gene transfer technology.
The biology and life cycle of lentiviruses will be described and recent
applications of lentivirus-based gene delivery systems will be presented. The
session will address issues related to translation of retrovirus-based gene
transfer to the clinic, covering the "how to’s" of the
review/approval process and production issues pertaining to retroviral vectors.
Chair: Robert G. Hawley, PhD
Speakers:
Christopher Baum, MD
ABCs of Retroviral Vectors
Robert G. Hawley, PhD
ABCs of Lentiviral Vectors
Richard Morgan, PhD
Clinical Translation of Retrovirus-Based Gene Delivery
|
| |
Education
Session ES101
Adenovirus Vectors
The goal of the
educational session on adenovirus vectors 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, 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.
Chair: Robin Parks, PhD
Speakers:
Andrea Amalfitano, DO, PhD
Multiply-Deleted Ad Vectors, Clinical Trials and Immunological Responses to
Vector Delivery
Philip Leopold, PhD
Adenovirus Entry and Tropism
Robin Parks, PhD
Adenoviral Vectors Deleted of All Viral Coding Sequences
|
| |
Education
Session ES102
AAV Vectors
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. We will discuss 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
Speakers:
Jeffrey S. Bartlett, PhD
Pathways of Transduction and Retargeting
J. Chiorini, PhD
AAV Serotypes
Matthew Weitzman, PhD
The AAV Life-Cycle and Production of Recombinant Vectors
|
| |
Education
Session ES103
Large DNA Virus Vectors
Large DNA viruses in
general have a high transgene capacity. Genes that are not strictly required for
virus replication can be replaced by foreign DNA to create replication-competent
or conditional vectors, e.g. for the selective killing of tumor cells or
vaccination. Replication-defective vectors are created by replacing genes that
are essential for virus replication or even all virus genes. In particular,
herpes simplex virus-based amplicon vectors and "gutless" adenovirus
vectors contain only the cis-elements required for replication and packaging of
the vector genome. Therefore, these vectors allow the insertion of genomic
sequences as well as cDNA. Furthermore, large transcriptional regulatory
sequences for cell type-specific expression, multiple transgenes, and genetic
elements from other viruses to create hybrid vectors may be used in a modular
fashion.
Chair: Cornel Fraefel, PhD
Speakers:
Stefan Kochanek, MD
Helper Dependent Adenovirus
Cornel Fraefel, PhD
Herpes Virus-Based Vectors for Gene Transfer/Therapy
Linda Gooding, PhD
Adenovirus and Immune Evasion
|
| |
Education
Session ES104
Non-Viral Vectors - Formulations
There is
continued interest in the development of non-viral vectors for gene therapy of a
variety of disease indications. Several synthetic gene transfer systems have
been described that exhibit good transduction activity following systemic,
intrapulmonary and intramuscular delivery. Maximal transfection activity is only
attained following systematic optimization of the formulations of these vector
systems. This education program will highlight considerations for formulation
development of non-viral vectors for use in the different routes of delivery.
Chair: Seng H. Cheng, PhD
Speakers:
Leaf Huang, PhD
Considerations for Systemic Delivery of Non-Viral Vectors
Louis C. Smith, PhD
Considerations for Gene Transfection of the Muscle Using Synthetic Vectors
Seng H. Cheng, PhD
Considerations for Non-Viral Mediated Gene Transfection of the Lung
|
| |
Education
Session ES105
Non-Viral Vectors - Applications
From DNA vaccines
to cancer therapy to therapeutic angiogenesis to tissue engineering (to name a
few) recent work has suggested that genes can be delivered effectively without
using viruses. This educational session will focus on potential clinical
applications of non-viral vectors.
Chair: Jeffrey
Bonadio, MD
Speakers:
Pamela Gehron Robey, PhD
Skeletal Stem Cells and Tissue Regeneration
Kristi Anseth, PhD
Biomaterials
|
| |
Education
Session ES106
Transgene Immunology
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: James M. Wilson, MD,
PhD
Speakers:
Margaret A. Liu, MD
Increasing or Decreasing Immune Responses for Different Gene Therapy
Clinical Applications
T-C Wu, MD, PhD
Innovative Strategies to Enhance DNA Vaccine Potency
|
| |
Education
Session ES107
Expression Cassette Design
This is a complex
subject, which can be subdivided into six components: the benefits of optimizing
expression; regulation of transcription; RNA stability and transport;
translation and protein processing; optimization of the transgene product; and
miscellaneous components including effect of vector backbone on expression
cassette, effect of expression cassette on vector backbone, multiple transgenes
(e.g. IRES, promoter interference), and role of tissue specific expression in
minimizing transgene product antigenicity.
Chair: Michael Kaleko, PhD
Speakers:
William Osborne, PhD
Title TBA
Volker Sandig, MD, PhD
Promoters and Transcripts - Upstream Determinants of Transgene Expression
|
| 5:30
pm – 6:45 pm |
Dinner
Break |
| 6:45
pm – 8:15 pm |
7
Education Sessions |
| |
Education
Session
ES110
Retrovirus Vectors
This session will
discuss the use of retroviruses and lentiviruses as vectors for gene therapy.
Speakers will describe the biology and life cycle of retroviruses, and review
the "state-of-the-art" of retrovirus-based gene transfer technology.
The biology and life cycle of lentiviruses will be described and recent
applications of lentivirus-based gene delivery systems will be presented. The
session will address issues related to translation of retrovirus-based gene
transfer to the clinic, covering the "how to’s" of the
review/approval process and production issues pertaining to retroviral vectors.
Chair: Robert G. Hawley, PhD
Speakers:
Christopher Baum, MD
ABCs of Retroviral Vectors
Robert G. Hawley, PhD
ABCs of Lentiviral Vectors
Richard Morgan, PhD
Clinical Translation of Retrovirus-Based Gene Delivery
|
| |
Education
Session ES111
Adenovirus Vectors
The goal of the
educational session on adenovirus vectors 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, 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.
Chair: Robin Parks, PhD
Speakers:
Andrea Amalfitano, DO, PhD
Multiply-Deleted Ad Vectors, Clinical Trials and Immunological Responses to
Vector Delivery
Philip Leopold, PhD
Adenovirus Entry and Tropism
Robin Parks, PhD
Adenoviral Vectors Deleted of All Viral Coding Sequences
|
| |
Education
Session ES112
AAV Vectors
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. We will discuss 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
Speakers:
Jeffrey S. Bartlett, PhD
Pathways of Transduction and Retargeting
J. Chiorini, PhD
AAV Serotypes
Matthew Weitzman, PhD
The AAV Life-Cycle and Production of Recombinant Vectors
|
| |
Education
Session ES113
Large DNA Virus Vectors
Large DNA viruses in
general have a high transgene capacity. Genes that are not strictly required for
virus replication can be replaced by foreign DNA to create replication-competent
or conditional vectors, e.g. for the selective killing of tumor cells or
vaccination. Replication-defective vectors are created by replacing genes that
are essential for virus replication or even all virus genes. In particular,
herpes simplex virus-based amplicon vectors and "gutless" adenovirus
vectors contain only the cis-elements required for replication and packaging of
the vector genome. Therefore, these vectors allow the insertion of genomic
sequences as well as cDNA. Furthermore, large transcriptional regulatory
sequences for cell type-specific expression, multiple transgenes, and genetic
elements from other viruses to create hybrid vectors may be used in a modular
fashion.
Chair: Cornel Fraefel, PhD
Speakers:
Stefan Kochanek, MD
Helper Dependent Adenovirus
Cornel Fraefel, PhD
Herpes Virus-Based Vectors for Gene Transfer/Therapy
Linda Gooding, PhD
Adenovirus and Immune Evasion
|
| |
Education
Session ES114
Non-Viral Vectors - Formulations
There is
continued interest in the development of non-viral vectors for gene therapy of a
variety of disease indications. Several synthetic gene transfer systems have
been described that exhibit good transduction activity following systemic,
intrapulmonary and intramuscular delivery. Maximal transfection activity is only
attained following systematic optimization of the formulations of these vector
systems. This education program will highlight considerations for formulation
development of non-viral vectors for use in the different routes of delivery.
Chair: Seng H. Cheng, PhD
Speakers:
Leaf Huang, PhD
Considerations for Systemic Delivery of Non-Viral Vectors
Louis C. Smith, PhD
Considerations for Gene Transfection of the Muscle Using Synthetic Vectors
Seng H. Cheng, PhD
Considerations for Non-Viral Mediated Gene Transfection of the Lung
|
| |
Education
Session ES115
Non-Viral Vectors - Applications
From DNA
vaccines to cancer therapy to therapeutic angiogenesis to tissue engineering (to
name a few) recent work has suggested that genes can be delivered effectively
without using viruses. This educational session will focus on potential clinical
applications of non-viral vectors.
Chair: Jeffrey
Bonadio, MD
Speakers:
Pamela Gehron Robey, PhD
Skeletal Stem Cells and Tissue Regeneration
Kristi Anseth, PhD
Biomaterials
|
| |
Education
Session ES116
NIH Grantsmanship
The goal of this
session is to acquaint participants with the grant review and funding process at
the NIH. Participants will hear from program staff, review staff and Study
Section members on what contributes to a successful grant application. Program
Staff will 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:
Sonia Skarlatos, PhD
Role of NIH Program Staff
Katherine Ponder, MD
A Reviewer’s Perspective on NIH Grants
Terry R. Bishop, PhD
NIH Support for Training Opportunities
Alec S. Liacouras, PhD
Role of Review Staff
|
| 8:30
pm – 10:00 pm |
8
Education Sessions |
| |
Education
Session
ES120
Liver Gene Transfer
The liver
is an excellent target for gene therapy because of the large number of
genetic diseases that involve liver proteins, the ready access of the
liver from the blood, the presence of receptors for most viral vectors on
the hepatocyte, and the fact that liver cells have a long lifespan. This
educational session will review the myriad of diseases that can be
approached with liver gene therapy. The ability of AAV, retroviral,
adenoviral, and plasmid vectors to transfer genes into the liver, as well
as the ability of RNA:DNA repair to modify the endogenous chromosome, will
be discussed. Finally, the mechanism of liver growth and development will
be reviewed, as long-term efficacy of gene therapy requires that either a
long-lived cell or a stem cell be transduced. This session will highlight
the outstanding potential for liver-directed gene therapy to permanently
correct congenital and acquired genetic disorders.
Chair: Katherine
Ponder, MD
Speakers:
Katherine Ponder, MD
Biology of the Hepatocyte and Other Cell Types of the Liver
Clifford J. Steer, MD
Non-Viral Approaches to Liver Gene Therapy - What's Treatable?
Mark Kay, MD, PhD
Viral Vectors for Liver Gene Therapy
|
| |
Education
Session ES121
Lung Gene Transfer
This
session will cover the recent advances in vector development for the
lungs, including retargeting of adenovirus vectors, novel adeno-associated
virus vectors, and retargeting of retroviruses to the lung. The session
will also cover some aspects of lung-specific expression and lung
toxicity. Clinical trials in lung gene therapy will be covered, including
current studies and some of the lessons learned from previous trials.
Chair: Joseph Zabner,
MD
Speakers:
Dongsheng Duan, PhD
Vectors for Gene Therapy to the Lungs
Ben-Gary Harvey, MD
Clinical Trials for Adenovirus in CF
Pamela L. Zeitlin, MD, PhD
Clinical Trials for Adeno-Associated Virus in CF
|
| |
Education
Session ES122
Cardiovascular Gene Transfer
Diseases of
the cardiovascular system comprise some of the commonest and most serious
health problems in our society. Gene therapy treatments are being
developed for many diseases of the heart and blood vessels. This session
will review the relevant basic biology of the cardiovascular system,
including the types of cells that could be modified by gene therapy and
their roles in pathological conditions. The advantages and disadvantages
of different vector systems used in the cardiovascular system will be
discussed, and an overview of possible applications will be presented.
Chair: Ronald G.
Crystal, MD
Speakers:
Ronald G. Crystal, MD
Vectors and Genes
Frank J. Giordano, MD
Experimental Models
Todd K. Rosengart, MD
Clinical Studies
|
| |
Education
Session ES123
Skin Gene TransferGene
therapy has the potential to treat many disorders of the skin, including
genetic diseases and acquired conditions, and the skin could be used to
deliver therapeutic proteins for other types of disorders. This session
will review the cell types and anatomy of the skin as it relates to gene
transfer strategies. The relative performance of different vector systems
in the skin will be discussed. Possible clinical applications of skin gene
transfer will be reviewed.
Chair: Gerald Krueger,
MD
Speakers:
Jonathan Vogel, MD
Achieving Persistent Gene Expression in the Skin: The Problem of
Targeting Keratinocyte Stem
Dennis Roop, PhD
The Challenge of Developing Gene Therapy for Dominantly Inherited
Diseases in a Regenerating Epithelium
|
| |
Education
Session ES124
Gene Transfer in Joints
Local
delivery of therapeutic genes to joints can be used for treatment of
arthritis, both rheumatoid and osteoarthritis, and repair of damaged
cartilage, ligaments, tendons and bone. The session will provide an
overview of diseases and disorders amenable to treatment by gene transfer
to joints. In addition, a summary of the approaches utilized for gene
transfer to joints, both viral and non-viral, will be presented. Finally,
the current status of clinical trials for gene therapy for joint diseases
will be addressed. In general, this session will provide an overview of
the current status and future of intra-articular gene transfer for
treatment of joint diseases and disorders.
Chair: Paul D. Robbins,
PhD
Speakers:
Christopher Evans,
PhD
Intra-articular Gene Therapy
Paul D. Robbins, PhD
Viral Gene Transfer to Joints
Raphael Hirsch, MD
Gene Therapy for Arthritis
|
| |
Education
Session ES125
Gene Transfer in the Eye
Methods for delivering transgenes to various ocular cell types will be
reviewed. Approaches for assessing transgene expression and function using
non-invasive techniques will be described. Illustrations of how different
gene therapy strategies have been used successfully to treat particular
ocular diseases will be provided. Predictions for future developments in
ocular gene therapy will be made.
Chair: Jean Bennett,
MD, PhD
Speakers:
Jean Bennett, MD, PhD
Delivery and Evaluation of Expression in the Eye and Gene Therapy for
Loss of Function Disease
John G. Flannery, PhD
Strategies Involving Delivery of Growth Factors as Rescue Agents and
Use of Ribozymes
Rajendra Kumar-Singh,
PhD
Ocular Gene Therapy Vectors and the Future to Improve Therapeutic
Efficacy
|
| |
Education
Session ES126
FDA/OBA Regulations
The session will give a general overview of regulatory issues and
procedures required for the conduct of clinical gene therapy trials. The
session in geared for individuals who are considering entering the
clinical arena and have not attended the Clinical Training 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.
Chair: Kenneth Cornetta,
MD
Speakers:
Kenneth Cornetta, MD
Submitting an IND and FDA Reporting
Terence Flotte, MD
RAC Submission and Oversight
Patrick Kelly, MD
Monitoring After Gene Transfer: The Requirements and Other Practical
Issues
|
| |
Education
Session ES127
Stem Cells
Stem cells have been a focus of interest over the past two years due to
the isolation of human embryonic stem (ES) cells and the discovery of
potential differentiation plasticity of adult-derived stem cells. In this
session, the pros and cons of ES and adult stem cells will be discussed
and some recent studies on stem cell plasticity will be reviewed. In
addition, issues concerning gene transduction of stem cells will be
presented.
Chair: Margaret Goodell,
PhD
Speakers:
Jane S. Lebkowski,
PhD
Human Embryonic Stem Cells: Applications for the Treatment of
Degenerative Diseases
Jan Nolta, PhD
Immunodeficient Mouse Models of Human Stem Cell Biology
Margaret Goodell, PhD
Adult-derived Stem Cells and Potential Differentiation Plasticity
|
|
|
|
Preliminary
Program