HUM-MOLGEN events: 3rd Cell & Gene Therapy Conference

Day 1 - Monday, September 12, 2016

7:00

Registration & Continental Breakfast

Keynote Presentation

KEYNOTE PRESENTATION

8:00

Clinical Development of Gene Therapy for Hemophilia B

Marcus Carr
Vice President Clinical Hematology
Rare Disease Research Unit
Pfizer

Pre-clinical Research

8:45

Hy Levitsky
Executive Vice President & Chief Scientific Officer
Juno Therapeutics

9:10

Vector Engineering to Overcome Barriers in Preclinical Gene Therapy for Proof-of-concept Studies

Guangping Gao
Professor & Director, Horae Gene Therapy Center
Professor of Microbiology & Physiology Systems
Penelope Booth Rockwell Professor in Biomedical Research
University of Massachusetts Medical School

Efficient and safe gene delivery is the key for gene therapy. Among all different viral vectors available for gene delivery to date, adeno-associated virus (AAV)–based vector hold great promise for its high efficiency, stability, and low immunogenicity/toxicity. AAV vector-mediated efficient and stable gene delivery is the team work of both viral capsid and vector genome. This presentation will describe our efforts in gene therapy vector optimization through viral capsid and vector genome engineering to accomplish proof-of-concept efficacious and sustained preclinical gene therapy in animal models as and to probe mechanisms for disease pathology and gene therapy.

9:35

Large Animal Models of Cardiovascular Diseases for Cell and Gene Therapy

Kiyotake Ishikawa
Assistant Professor
Icahn School of Medicine

Cardiovascular disease remains the leading cause of hospitalization and mortality in the US, despite recent pharmaceutical advancements and improved health care. Gene and stem therapy have emerged as promising approaches to change this paradigm and active research at the bench demonstrates promising results. In order to successfully translate these positive results toward the clinic, thorough evaluation of efficacy as well as safety is essential. To this end, several large animal models of cardiovascular disease that recapitulate clinical phenotypes have been developed in our laboratory. Representative models will be presented together with a recent successful example study using one of the models.

10:00

Morning Networking Break

10:30

The Future of Biotherapeutics

Michael Naso
Scientific Director, Janssen Biotherapeutics
Janssen R&D

We are rapidly progressing our basic understanding of molecules and pathways that drive health and disease. The logical outcome of these efforts will be the identification of therapeutic intervention strategies that are specific for those pathways that are at the heart of the disease state. As target identification and validation efforts progress, we will be challenged by the current limitations of our therapeutic drug platforms. Small molecule drugs and biologics (large molecules) each have several significant issues with regard to the type of molecules they can effectively modulate, as well as, the costs associated their discovery and development. Gene therapies have the potential to accommodate all of these limitations, and could eventually replace current small molecule and biologics as the therapeutic platform of choice.

Emerging Technologies

10:55

Next Gen HSV Vectors for Persistent Transgene Expression in the Nervous System

Joseph Glorioso
Professor, Microbiology & Molecular Genetics
University of Pittsburgh

Gene therapy for nervous system disease requires long-term, targeted transgene expression in selected nerve cell populations. In many cases high capacity vectors are needed to accommodate multi- or large gene payloads. HSV is a neurotropic human virus that persists in neurons, however virus toxicity and failure to achieve robust durable transgene expression has proven difficult to achieve. We will describe a new generation of high capacity, non-cytotoxic defective HSV-1 vectors that exploit natural viral insulator sequences to achieve robust expression of reporter genes in multiple brain regions in rodents. These vectors are deleted for the reiterated joint sequences (~15kb) flanking the UL and US unique components and functionally devoid of all viral immediately early genes. Durable transgene expression was achieved in both neuronal and non-neuronal cells. Transgene expression could be highly restricted to specific nerve cell populations using both transductional and transcriptional targeting. These new generation HSV vectors fill a void in vector technology for gene therapy that can be applied to the treatment of complex degenerative disease

11:20

Gene Switches for Gene Therapies

Ian Phillips
Director, Center for Rare Disease Therapies
Keck Graduate Institute of Applied Life Sciences

Gene therapies repair or replace mutated genes, stem cells replace entire cells. While gene therapies are becoming a reality, stem cells still have barriers to overcome. We have developed gene switches that can turn on and off transgene expression. The gene switch offers something new and advanced for gene therapy and stem cell therapies. Unlike CRISPR-cas9, Talens and zinc fingers which are irreversible, our gene switches are reversible (Phillips 2012).They could supply genes when needed.

For example we built a gene switch that senses oxygen levels in tissue. Under hypoxia at the cellular level, the gene switch detects low oxygen and switches on a hybrid protein that activates an upstream promoter sequences of an inserted gene. The effector genes are varied depending on the purpose : We have tested the gene switch for Myocardial ischemia, with the heme oxygenase 1 gene being activated to prevent apoptosis and reduce inflammation. .We used the gene switch to increase survival of autologous mesenchymal stem cells (MSCs) after transplantation (Tang et al, 2005). Normally 90% of MSCs die within 48 hours of transplantation but MSCs protected by the gene switch (“The Vigilant Vector”) functioned for at least 4weeks after transplantation in the heart .

The gene switch could aid automatic healing. During the Iraq war the US Army and DRTA supported the development of our gene switch as a “ Vigilant hemostat” a concept to cease hemorrhage in multiple internal wounds in combat before the wounded soldier could be rescued. The gene switch started automatically to stop bleeding with Factor 7 gene. The experiments ended with the war ending but we hope to pursue the idea of automatic healing with the newly awarded ( 2015) US patent (US patent #9,040,676).

11:45

Stephen Chang
Vice President, Research & Development
NY Stem Cell Foundation

12:10

Lunch on Your Own