2015 Archived Content
Gene therapy has seen its fair share of ups and downs, and yet has continued to progress relentlessly. While the challenges and risks associated with it still remain, there is a new and better understanding of how genes can be effectively manipulated and delivered. With the rise of gene editing tools and enhanced knowledge of targeted delivery, gene therapy may finally achieve its true potential. Gene Therapy Breakthroughs will bring together leading scientists, clinicians, executives and experts who can collectively disperse information on the impact of recent findings on gene therapy and how it can be applied. This conference will highlight scientific breakthroughs, use of innovative technologies and approaches to tackle gene delivery and the translational challenges, and bring together the right people to discuss existing challenges and future opportunities in this field.
Final Agenda
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Tuesday, September 22
7:00 am Registration and Morning Coffee
8:00 Chairperson’s Opening Remarks
Charles P. Venditti, M.D., Ph.D., Head, Organic Acid Research Section, Senior Investigator, National Human Genome Research Institute, National Institutes of Health
8:10 KEYNOTE: Next Generation AAV Vectors and Their Use in Rare Diseases
James Wilson, M.D., Ph.D., Professor, Department of Pathology and Laboratory Medicine, University of Pennsylvania
Human gene therapy is a 30+ year “work-in-progress”
that is finally yielding success in the clinic. Vectors based on recombinant
viruses such as adeno-associated virus and lentivirus are being developed in
the biopharmaceutical industry as products for diseases with substantial unmet
need. I will discuss the state of the human gene therapy using current
technologies as well as future refinements and novel applications such as in
gene editing.
9:10 Genotoxicity of AAV in Murine Models: Implications for Human Gene Therapy
Charles P. Venditti, M.D., Ph.D., Head, Organic Acid Research Section, Senior Investigator, National Human Genome Research Institute, National Institutes of Health
The safety of AAV as a vector has been questioned by several studies that have documented hepatocellular carcinoma (HCC) after AAV gene delivery in mice. In this talk, the experiments that have examined AAV genotoxicity will be reviewed and interpreted in the context of more recent genomic analyses that have widely surveyed the integration of AAV vectors. Comments on preclinical study design as it relates to AAV genotoxicity will be offered.
9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
10:25 Immune Responses in AAV Vector-mediated Gene transfer, Challenges and Potential Solutions
Federico Mingozzi, Ph.D., Team Leader, Genethon and Associate Professor, University Pierre and Marie Curie-Paris, France
Studies on AAV vector immunogenicity in human trials
and in animal models of gene transfer boosted our knowledge on the mechanisms
of AAV recognition by the host immune system. In some cases, this knowledge has
been successfully exploited in the clinic, for example to develop strategies modulate
cell-mediated immune responses directed against transduced cells, resulting in long-term
transgene expression. Future work will have to focus on better understanding
the determinants of AAV vector immunogenicity and on the remaining important
hurdles associated with immunity and AAV vectors, such as the ability to
overcome antibody responses to the capsid in the context of vector
re-administration.
10:55 AAV-Mediated Therapy to Target Neuromuscular Dysfunction in Pompe Disease
Darin Falk, Ph.D., Assistant Professor, Department of Pediatrics, Powell Gene Therapy Center, University of Florida
Patients with Pompe disease experience profound muscle weakness resulting in respiratory and movement difficulties. Recent evidence suggests this weakness may result from the severe pathology observed within the peripheral nerve and neuromuscular junction. The current therapy for Pompe disease does not reach the central nervous system and limits therapeutic potential. Our recent work uses AAV vectors to simultaneously target the neuronal and skeletal muscle pathology in Pompe disease to restore neuromuscular function.
11:25 AAV Clinical Success and Vector Development, a Process That Goes Hand in Hand
R. Jude Samulski, Ph.D., Professor, Department of Pharmacology and Director, Gene Therapy Center, University of North Carolina-Chapel Hill
This presentation
will provide a current perspective on the progression of AAV for gene therapy
from discovery to the clinic. We will focus on next generation delivery
approaches based on basic science and understanding and vector optimization for
improved efficacy and successful clinical applications.
12:10 pm Q&A with session speakers
12:25 Lunch on Your Own
1:15 Refreshment Break in the Exhibit Hall with Poster Viewing
1:50 Chairperson’s Remarks
Peter French, Ph.D., CEO and Managing Director, Benitec Biopharma Ltd.
2:00 Combining Gene Therapy and Gene Silencing for Transformational Therapeutics
Peter French, Ph.D., CEO and Managing Director, Benitec Biopharma Ltd.
Benitec’s ddRNAi technology combines the specificity of gene therapy vectors with the power of RNA interference to produce novel therapies for serious life threatening diseases. ddRNAi works thorough DNA constructs that continuously silence the disease-associated genes for the lifetime of the cell, allowing for single administration treatments and cures. Benitec’s pipeline includes hepatitis C, hepatitis B, non-small cell lung cancer, wet AMD and oculopharyngeal muscular dystrophy.
2:45 The Many Approaches of Gene Therapy for Liver Disorders
Clifford Steer, M.D., Professor of Medicine and Genetics, Cell Biology, and Development; Director, Molecular Gastroenterology Program, University of Minnesota Medical School
Liver plays a major role in many inherited and acquired genetic disorders. Research efforts have been intensified towards the development of targeted gene therapies using novel genetic tools, such as the ZFNs, TALENs and CRISPRs, as well as non-viral vectors, such as Sleeping Beauty, piggyBac transposons and PhiC31 integrase. While each of these methods utilizes a distinct mechanism of gene modification, all of them are dependent upon the efficient delivery of DNA and RNA into liver cells.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Winner Announced
4:10 Nucleic Acid Delivery Systems for RNA Therapy and Gene Editing
Daniel Anderson, Ph.D., Professor, Department of Chemical Engineering, Institute for Medical Engineering & Science, Harvard-MIT Division of Health Sciences & Technology and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Here we describe our work on high throughput methods for developing and characterizing RNA delivery and gene editing systems. Libraries of degradable polymers and lipid-like materials have been synthesized, formulated and screened for their ability to deliver RNA, both in vitro and in vivo. A number of delivery formulations have been developed with in vivo efficacy, and show potential therapeutic application for the treatment of genetic disease, viral infection, and cancer.
4:40 Next Generation Gene Therapy: Genome Editing
Matthew Porteus, M.D., Ph.D., Associate Professor, Pediatrics, Stanford University School of Medicine
There are now estimated to be 10,000 diseases caused by mutations in single genes (monogenic diseases). Curative therapy for these diseases would be based on treating these diseases at their foundation-by genetically modifying the genome. Genome editing now provides a powerful mechanism to precisely engineer the genome with nucleotide precision, true precision therapy, and this talk will focus on both the various tools available for genome editing and ways that the genome can be edited for therapeutic purposes.
5:10 Interactive Breakout Discussion Groups
This interactive session provides conference delegates and speakers an opportunity to choose a specific roundtable discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.
New Developments and Applications of AAV Vectors
Moderators:
R. Jude Samulski, Ph.D., Professor, Department of Pharmacology and Director, Gene Therapy Center, University of North Carolina-Chapel Hill
Darin Falk, Ph.D., Assistant Professor, Department of Pediatrics, Powell Gene Therapy Center, University of Florida
- Optimizing Design and Delivery of AAV Vectors
Addressing Safety Concerns in Gene Therapy
Federico Mingozzi, Ph.D., Team Leader, Genethon and Associate Professor, University Pierre and Marie Curie-Paris, France
- What are the most important issues of in vivo
gene transfer in terms of immune responses directed against AAV vectors;
- When do we need to use immunosuppression in gene
transfer;
- What are the most promising strategies being
proposed to overcome the issue of anti-capsid antibodies?
- Is transgene immunogenicity a concern for gene
transfer at all?
Combining Gene Editing and Gene Therapy
Moderators:
Matthew Porteus, M.D., Ph.D., Associate Professor, Pediatrics, Stanford University School of Medicine
Clifford Steer, M.D., Professor of Medicine and Genetics, Cell Biology, and Development; Director, Molecular Gastroenterology Program, University of Minnesota Medical School
- Guidelines on choosing gene therapy versus gene editing
- How concerned should we be about off-target effects?
- Delivery, delivery, delivery...it is here to stay and more important than ever
- What exists after CRISPR and TALENs?
6:10 Welcome Reception in the Exhibit Hall with Poster Viewing
7:15 Close of Day
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Wednesday, September 23
7:30 am Registration and Morning Coffee
8:00 Chairperson’s Remarks
Jaquelin Dudley, Ph.D., Professor, Department of Molecular Biosciences, The University of Texas at Austin
8:10 Using Retroviruses to Easily Increase Gene Expression
Jaquelin Dudley, Ph.D., Professor, Department of Molecular Biosciences, Center for Infectious Disease, and Institute for Cellular and Molecular Biology, The University of Texas at Austin
We recently described that transfection of lentiviral or gammaretroviral vectors into several different mammalian cell types increased expression of a co-transfected gene relative to standard plasmid vectors without changing levels of most endogenous cellular proteins (termed superinduction). Superinduction was not dependent on the cell type or species, the type of reporter gene, or the method of transfection. This has broad applications for the design of retroviral vectors for transfections, DNA vaccines, and gene therapy.
8:40 Ultrasound-Mediated Gene Delivery (UMGD): Applications in Cardiovascular Medicine
Howard Leong-Poi, M.D., Associate Scientist, Keenan Research Centre for Biomedical Science, and Associate Professor, Medicine/Cardiology, St. Michael’s Hospital, Toronto
UMGD is a non-invasive gene transfer technique, utilizing high power ultrasound and gene-bearing carrier microbubbles. Despite modest transfection efficiency, its high organ/tissue specificity and repeatability make it an attractive therapeutic option. UMGD has been used in a variety of in vivo applications, including cardiac and skeletal muscle. This talk will focus on cardiovascular applications, including UMGD for therapeutic angiogenesis in chronic ischemia, and for heart failure and acute myocardial infarction.
9:10 AAV-mediated Gene Therapy for Benign Tumors
Xandra Breakefield, Ph.D., Professor, Department of Neurology and Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School
Tuberous sclerosis and neurofibromatosis are caused by loss of tumor suppressor genes, with tumors forming throughout the body and nervous system. These tumors can compromise normal functions and cause pain due to compression of tissues through their expanding volume. Gene replacement and other constructs can be delivered systemically and across the blood-brain barrier to reduce tumor size.
9:40 Coffee Break in the Exhibit Hall with Poster Viewing
10:25 Human Clinical Trials of AAV-Based Based Gene Therapies for Orphan Ocular Disorders
Stephen W. Potter, Chief Business Officer, AGTC
AGTC is a clinical-stage biotechnology company that uses its proprietary gene therapy platform to develop AAV-based gene therapy products for severe inherited orphan diseases in ophthalmology. AGTC expects initial data in human subjects for its lead programs, for the treatment of X-linked retinoschisis and achromatopsia, during the second half of 2015.
10:55 Targeting the Inflammasome Signaling in a Mouse Model of a Geographic Atrophy: A Gene Therapy Approach
Cristhian J. Ildefonso, Ph.D., Senior Postdoctoral Associate, Laboratory of Dr. Alfred S. Lewin, Molecular Genetics & Microbiology, University of Florida College of Medicine
Geographic Atrophy (GA) is associated with oxidative stress and inflammation driven by the inflammasome signaling pathway. We developed and characterized AAV vectors to deliver secretable and cell-penetrating proteins targeting this pathway. These vectors are being tested in a GA mouse model.
11:25 Enjoy Lunch on Your Own
12:55 pm Plenary Keynote Program
2:40 Refreshment Break in the Exhibit Hall with Poster Viewing
3:25 Close of Conference
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