Education Session: 120
3:30 pm to 5:00 pm
Emerging Field Review: Genomic Basis of Human Disease

This program will be presented by three established investigators at the NIH National Human Genome Research Institute and will highlight active research programs of direct relevance to the field of gene and cell based therapies. The topics to be covered include: 1) The Genomics Landscape Circa 2010, 2) The ClinSeq Project: Piloting Genome Sequencing for Research in Genomic, and 3) The Undiagnosed Diseases Program.

Chair
Paul B. McCray, Jr., MD

Speakers
Eric D. Green, MD, PhD
The Genomics Landscape Circa 2010

Leslie G. Biesecker, MD (Materials Unavailable)
Large Scale Sequencing and Hypothesis-Generating Clinical Research

William A. Gahl, MD, PhD
The Undiagnosed Diseases Program

Education Session: 121
3:30 pm to 5:00 pm
Emerging Field Review: Regulatory RNAs

About a decade ago, it became clear that RNA has a widespread, general role in gene regulation. At least part of this regulation is mediated through a mechanism termed RNA interference (RNAi). The first talk will discuss the basic principles of RNAi and the biology of the small RNA species which mediate RNAi. The discovery of RNAi has opened up new avenues in genetic engineering which will be covered by the subsequent talks: Delivery of a small interfering RNA (siRNA) or an artificial microRNA (miRNA) with a specific sequence directed against an endogenous mRNA can result in potent knockdown of any gene of interest. Conversely, endogenous regulatory RNAs can be exploited as an additional layer of regulation to restrict the expression of an exogenously introduced transgene to cells of a specific tissue origin, lineage or
differentiation state. Finally, as miRNAs are increasingly being implicated in human disease, technologies that allow their manipulation (knockdown and overexpression) become relevant.

Co-Chairs
Alfred Lewin, PhD
Bernhard Gentner, MD

Speakers

Brian D. Brown, PhD
The Biology and Application of Regulatory RNAs

Ryan L. Boudreau, PhD
RNAi-based Strategies for Silencing Disease

Bernhard Gentner, MD
How to Study and Exploit microRNAs for Gene Therapy

Education Session: 122
3:30 pm to 5:00 pm
Topical Review: Cell Therapy

Chair
Edwin M. Horwitz, MD, PhD

Speakers
Edwin M. Horwitz, MD, PhD (Materials Unavailable)
Fundamentals of Cell Therapy

Peter Johnston, MD, FACC
Stem Cell Therapy for the Heart

Dao Pan, PhD
Cell and Gene Therapy for CNS Abnormalities in Lysosomal Storage Disorders

Education Session: 123
3:30 pm to 5:00 pm
Topical Review: Gene Therapy for Eye Diseases

Recent successes in viral vector-based gene therapy clinical trials underscore the potential of gene therapy as a means to provide definitive solutions for currently incurable ocular diseases. This session will focus on the basic biology and vector development for ocular diseases. In addition, it will provide recent updates on novel strategies in vector design, as well as  the status and prospects of gene therapy clinical trials for ocular diseases.

Co-Chairs
Peter A. Campochiaro, MD
Tal Kafri, PhD

Speakers
Peter A. Campochiaro, MD
Overview of Gene Therapy for Ocular Diseases

John G. Flannery, PhD (Materials Unavailable)
Evolution of AAV Vectors for Ocular Gene Therapy

Bill Hauswirth, PhD
AAV Vector Considerations for the Retina

Education Session: 124
3:30 pm to 5:00 pm
Topical Review: Stem Cell Basics

In order for stem cells to fulfill their potential as viable cell transplant/gene transfer therapeutics, it will be necessary to understand the process of stem cell self-renewal to obtain sufficient cell numbers to be applicable for transplant. Additionally, the genes/factors involved in differentiating these pluripotent cells down specific lineage pathways will also be crucial in the development of a transplantable therapeutic. The speakers in this session will address these important issues that not only provide further insight into organ and tissue development but also open up therapeutic avenues of practical application of these cells in regenerative medicine.

Chair
William F. Goins, PhD

Speakers
G. Ian Gallicano, PhD
Stem Cells: Past, Present, Future

David F. Stroncek, MD
Gene and MicroRNA Expression in Human Embryonic Stem Cells

Ming Zhan, PhD
Computational Biology Studies to Decipher Molecular Mechanisms Controlling Embryonic Stem Cell Pluripotency

Education Session: 130
5:30 pm to 7:00 pm
Emerging Field Review: Progress Towards Using ES/iPS Cells for Regenerative Medicine

The excitement over embryonic stem cells and induced pluripotent stem cells is that they are a potential source of cells for tissues in which tissue specific stem cells have either not been identified, not easily isolated, or not easily expanded.  That pluripotent stem cells can now be generated from somatic cells, without the destruction of an embryo, removes a major ethical barrier to their use.  Nonetheless, a continued barrier to the translation of pluripotent stem cells to clinical use is to expand and differentiate them in  both a safe and quantitatively sufficient manner that they can be used for tissue specific regenerative medicine applications.  This educational session will focus on the progress that has been made in generating sufficient numbers of safe tissue specific cells towards this end.

Chair
Matthew H. Porteus, MD, PhD

Speakers
Ronald D.G. McKay, PhD (Materials Unavailable)

Elias T. Zambidis, MD, PhD
Generation of HSC and Red Blood Cells from Normal and Hemoglobinopathic iPSC

Evan Y. Snyder, MD, PhD, FAAP (Materials Unavailable)
Cross-Talk and Developmental Programs in Stem Cell Biology – A Key to Regenerative Medicine

Education Session: 131
5:30 pm to 7:00 pm
Emerging Field Review: Targeted Integration

Uncontrolled insertion of foreign DNA into the human genome may have deleterious consequences, and is a serious safety concern in the clinical application of gene therapy. New molecular tools are being developed to target transgene integration to specific sites in the genome and increase the frequency of homologous recombination, with the purpose of achieving gene correction or replacement in the original genomic environment. These advances include the use of Zn-finger nucleases and homing endonucleases, and the delivery of homologous recombination cassettes by viral and non-viral vectors. They will be discussed in the context of developing better and safer gene transfer technology.

Chair
Fulvio Mavilio, PhD

Speakers
J. Keith Joung, MD PhD (Materials Unavailable)
Engineered Zinc Finger Nucleases for Targeted Genome Modification

Andrew M. Scharenberg, MD
Homing Endonucleases as Tools for Targeted Integration

David W. Russell, MD, PhD (Materials Unavailable)
 AAV-Mediated Gene Targeting

Education Session: 132
5:30 pm to 7:00 pm
Topical Review: Gene Delivery to the Heart

Heart disease is one of the leading causes of morbidity and mortality worldwide.  While molecular causes are known for many heart diseases, it requires effective heart gene delivery methods to translate these findings into therapy.  Because of the dynamic nature of the heart physiology and the unique anatomic location, cardiac gene transfer 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 porcine models.

Chair
Dongsheng Duan, PhD

Speakers
Dongsheng Duan, PhD
Overview of Heart Gene Transfer in Mice

Roger J. Hajjar, MD (Materials Unavailable)
Gene Therapy for Heart Failure: New Targets and New Vectors

Charles R. Bridges, MD, ScD
Methods for Cardiac Gene Delivery

Education Session: 133
5:30 pm to 7:00 pm
Topical Review: Immunotherapy of Cancer

The immune system can be properly modified to eradicate cancer. Currently, effector molecules, such as monoclonal antibodies and cells such as tumor-reactive lymphocytes, are able to selectively target and eliminate tumors, may be isolated and/or engineered. The potency of cellular adoptive immunotherapy has been revealed by persistent and complete clinical responses obtained with by the transfer of allogeneic T lymphocytes in the context of allogeneic hemopoietic cell transplantation (allo-HSCT) and by the transfer of autologous tumor specific cytotoxic T lymphocytes (CTLs) in cancer patients. Major hurdles limiting adoptive T cell therapy relate to toxicity (ie: graft-versus-host disease-GvHD in allo-HSCT), feasibility and efficacy (ie: difficulty in expanding rare, high-avidity tumor-specific CTLs). Gene transfer technologies may allow to overcome all these hurdles. The transfer of tumor-specific TCR or chimeric antigen receptors (CARs), confers tumor-specificity and activity to autologous T cells. The transfer of a suicide gene into allogeneic lymphocytes allows to tame toxicity of allogeneic lymphocytes. In this session, we will discuss clinical results, challenges and advances recently made to improve the potency and specificity of adoptive immunotherapy with genetically modified lymphocytes to treat cancer.

Chair
Chiara Bonini, MD

Speakers
Richard A. Morgan, PhD
Using Engineered T Cells for the Treatment of Cancer

Gianpietro Dotti, MD
Car-Based Gene Transfer in T Lymphocytes

Chiara Bonini, MD
T-Cell Based Gene Therapy in Hematopoietic Stem Cell Transplantation

Education Session: 134
5:30 pm to 7:00 pm
Topical Review: Pre-existing Immunity to Gene Transfer Vectors

Many viral gene therapy vectors are derived from parent viruses that are present in the human population. Pre-existing immunity to such vectors in form of antibodies and memory B and T cell responses can severely hamper gene transfer in humans. This session will review basic aspects of B cell biology, prevalence of antibodies to DNA viruses (AAV and adenovirus) in the human population, and CD8+ T cell responses to AAV capsid in humans.

Chair
Roland W. Herzog, PhD

Speakers
Michael Cancro, PhD
The Persistent Problem of B Cell Memory

Luk Vandenberghe, PhD
B-cell Immunity to Viral Vectors

Katherine A. High, MD (Materials Unavailable)
Human T Cell Responses to AAV Capsid