Short Courses | Day 1 | Day 2 | Download Brochure

12:00 pm Registration Open 

2:00 Chairperson’s Remarks
Mark A. Kay M.D., Ph.D., Professor, Departments of Pediatrics and Genetics, Stanford University 

2:05 Systemic RNAi Therapeutics for Treating Infection
Mark A. Kay M.D., Ph.D., Professor, Departments of Pediatrics and Genetics, Stanford University 
Gene transfer vectors expressing shRNAs to target specific tissues have been utilized for treating different diseases. Recombinant AAV vectors expressing shRNAs have been shown to be effective in reducing hepatitis B viral replication in a transgenic mouse model. Interestingly, over expression of shRNAs can be toxic and even lethal because it interferes with normal mi-croRNA processing. The rate-limiting steps in mammalian tissues as well as effective strategies to maintain a high therapeutic index will be discussed.

2:35 Delivering RNAi Therapeutics
Muthiah Manoharan Ph.D., Vice President, Drug Discovery, Alnylam Pharmaceuticals

3:05 Delivery of Therapeutic RNA Interference into the GI tract
Johannes Fruehauf, M.D., Ph.D., Vice President, Research, Cequent Pharmaceuticals Inc.
Transkingdom RNA interference, (tkRNAi), uses nonpathogenic bacteria that are modified to act as manufacturers and carrier vehicles of interfering RNA against genes of interest. Activity has so far been shown across a wide range of targets. APCmin mice are a genetic model of human colon cancer. Here we show, that chronic oral treatment of APCmin mice (n=38) with tkRNAi bacteria resulted in a significant decrease of polyp formation through blockage of the CTNNB1 pathway in the gut. These findings open the possibility of developing RNAi-based drugs for organs and tissues outside of the areas targeted, including the gastrointestinal tract, genitourinary tract, and the skin.

3:35 Technology Spotlight (Sponsorships Available)

3:50 Networking Refreshment Break, Poster and Exhibit Viewing

4:30 Construction of phi29 DNA-Packaging Motor for Applications in Nanotechnology, Therapy, Diagnosis, and Drug Delivery
Peixuan Guo, Ph.D., Chair in Biomedical Engineering and Director of NIH Nanomedicine Development Center, University of Cincinnati 
Bacterial virus phi29 packaging RNA (pRNA) is an ATP-binding component of the DNA packaging motor. Its unique feature to form dimer, trimer, hexamer and patterned superstructures via the interaction of two interlocking loops makes it a promising tool in nanomedicine. Replacement or insertion of the 5’/3’helical domain with siRNA, ribozyme and receptor-binding aptamer does not interfere with the formation of the multimers, making it a novel vehicle for targeted therapy, pathogen detection and drug delivery. The chimeric siRNA/pRNA complex induced apoptosis in specific cancer cells, as tested in both cell culture and in animal trials. 

5:00 In vivo Imaging of siRNA Delivery and Silencing in Tumors
Anna Moore, Ph.D., Associate Professor, Department of Radiology and Director, Molecular Imaging Laboratory, Massachusetts General Hospital
The fast developing field of RNA interference requires monitoring of siRNA delivery to targeted organs and evaluating the efficiency of target gene silencing. Molecular imaging techniques represent a powerful tool for real-time non-invasive monitoring of various events at a near microscopic level and have superiour advantages over conventional in vitro and cell culture research techniques in biology. Therefore, molecular imaging approach fits perfectly to fulfill the need to monitor siRNA delivery and provides information in a fast, reproducible and non-invasive manner. This presentation will summarize the existing information on various imaging modalities and their application for siRNA imaging. 

5:30 Close of Day

Wednesday, June 11

7:00 am - 4:00 pm Registration Open 

7:30am Facilitated Break-Out Discussion Groups & Morning Coffee

8:15 Chairperson’s Remarks

8:50 Statistical and Computational Pharmacogenetics: Detecting Genes for Drug Response 
Ronging Wu, Ph.D., Professor, University of Florida Research Foundation Professor, Statistics,
University of Florida
I will present a conceptual framework for computing genes and genome for drug response by integrating mathematical and chemical aspects of drug reactions in the body. With this frame-work, specific DNA sequence variants can be identified on the basis of the test of a few parameters that define the shape and pattern of drug responses, which thus enhances the precision of parameter estimation as well as biological and clinical relevance in pharmacogenetic and pharmacogenomic research.

9:20 Clotting, Cascades, and Computers - Systems Biology in Personalized Medicine
Michael Roehrl, M.D., Ph.D., Pathology and Laboratory Medicine, Massachusetts General Hospital 
The human blood clotting system is a complex and highly regulated network of biomolecular interactions. Data from careful biochemical measurements can be integrated into quantitative and predictive computational models of blood coagulation. Millions of patients receive the oral anticoagulant Coumadin to prevent fatal thromboembolic events. Personalized Coumadin dosing is both cumbersome and expensive and potentially dangerous. Coumadin is among the top 10 drugs with the largest number of serious adverse event reports submitted to the FDA. We show how a novel Systems Biological approach can be used in the clinical setting to personalize Coumadin dosing and to achieve safe therapeutic goals. 

9:50 Networking Coffee Break, Poster and Exhibit Viewing

10:45 Identify Pathway Specific Gene Signatures for Cancer Prognosis using Gene Expression Profiling Data
Dan Li, Ph.D., Principle Research Scientist, Informatics, Integrative Biology, Eli Lilly and Company
Neoplastic transformation and progression is driven by deregulated cellular pathways that control cell fate, growth, differentiation and survival. Although significant progress has been made to identify and characterize oncogenes, tumor suppressors and the molecular pathways that they regulate, it remains largely unclear what pathways play a critical role in the development of different tumor types. Post-genomic era technology in gene expression profiling has provided a powerful tool to study gene regulations in cancers at the molecular level. In this study, we developed and applied a novel approach to derive gene signatures for cancer prognosis in the context of known biological pathways. 

11:15 Genome-wide Transcriptional Fingerprinting of Hepatotoxicity Regulatory Networks Using Multiplex Parallel High Throughput ChIP-on-Chip Assays 
Jeff Falk, Ph.D., Director, Technology Applications, Molecular Biology, Aviva Systems Biology
A genome-wide transcription factor mapping consortium is currently being assembled facilitate global identification of key toxicity and disease-related networks and biomarkers by providing reference fingerprints of transcription factor-mediated pathway modulations in key tissues that can then be compared with similar profiles derived from disease-related or therapeutic com-pound treated samples. We will describe the initial phase of experiments utilizing our next generation ChIP-on-chip technology for mapping of transcriptional networks that pinpoint critical pathways and biomarkers associated with hepatotoxicity. 

11:45 Systems Biology of Melanoma
William Kaufmann, Ph.D., Professor, Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill
I propose to describe a model of human carcinogenesis that is based upon the interaction of an external stress (sunlight) with mutations in the MAPK signaling pathway in melanocytes to cause deletions in the CDKN2A tumor suppressor locus that encodes p16INK4A and ARF. Systems biology approaches to the model include generation of genetic and physical interaction networks to model the DNA damage response, global analysis of gene expression to identify melanoma subtypes, and mathematical models of nucleotide excision repair and G2 DNA damage checkpoint responses.

12:15 pm Close of Morning Session

12:30 Luncheon Technology Workshops (Sponsorships Available) or Lunch on Your Own

1:45 Chairperson’s Remarks

1:50 A Synthetic Gene Delivery System for IL-12: From Bench to Clinic 
Khursheed Anwer, Ph.D., Vice President, Research & Development, Expression Genetics, Inc. 
This presentation describes the discovery and development of a synthetic lipopolymer for gene delivery of IL-12 for cancer. Synthesis, formulation, scale-up, stability, animal safety/toxicity, biodistribution and results from two clinical trials in ovarian cancer patients will be discussed. Application for additional cancer indications will also be described briefly.

2:20 Gene Therapy Development using HIV as a Specific Example
Geoff Symonds, Ph.D., Senior Research Director, Global Product Leader, HIV Gene Therapy, Johnson & Johnson Research 
Gene Therapy represents a different treatment paradigm and the presentation will address the development process within the setting of big Pharma using the specific example of Gene Ther-apy for HIV. Similarities and differences to small molecule and biologics development will be discussed, as well as the means by which Gene Therapy can be ‘incubated’ to a point that it can stand alone. 

2:50 Evidence of Neuroregeneration using Vascular Endothelial Growth Factor Zinc Finger Protein Activator (SB-509) in Patients with Diabetic Neuropathy: A Chronic Degenerative Polyneuropathy
Ely Benaim, M.D., Vice President, Clinical Affairs, Sangamo BioSciences, Inc.
Twenty four patients were treated with either VEGF Zinc finger protein plasmid DNA(SB-509 n=12) or placebo (n=12) at a single treatment and were followed for clinical neurologic im-provement for 6 months. There was a statistically significant 25% improvement in Quantitative Sensory Testing in the lower extremities. Motor and Sensory Nerve Conduction Velocities showed a trend for improvement in a clinically relevant magnitude. This study provided the basis for two Phase 2 trials in mild to moderated and moderate to severe Diabetic Neuropathy.

3:20 Networking Refreshment Break, Last Chance for Poster and Exhibit Viewing

4:00 Poster Awards in the Exhibit Hall

Collaboration Across Areas of Expertise

5:30 Close of Conference

Targeting Gene Therapy Continued | Short Courses | Day 1 | Day 2 | Download Brochure