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TUESDAY, JUNE 9
12:00 - 2:00 pm Registration for RNAi for Therapeutic Indications and RNAi for Target Identification and Validation Conferences
Moderator: Bob D. Brown, Ph.D., Senior Vice President, Research, Dicerna Pharmaceuticals Corp.
Participants:
Arthur M. Krieg, M.D., Chief Scientific Officer, Research Technology Center, Pfizer Inc.
Elena Feinstein, M.D., Chief Scientific Officer, Quark Pharmaceuticals Inc.
Klaus Giese, Ph.D., Chief Scientific Officer, Silence Therapeutics PLC
Thomas Singer D.A.B.T. Global Head of Non-Clinical Safety, F. Hoffmann-La Roche AG
3:35 Sponsored Presentation (Opportunity Available)
3:50 Networking Refreshment Break Poster and Exhibit Viewing
Participants:
Kathleen M. Williams, Ph.D, J.D., Intellectual Property Attorney, Partner, Edwards Angell Palmer & Dodge LLP
Rochelle K. Seide, Ph.D., Senior Counsel, Schwegman, Lundberg & Woessner, P.A.
Steven L. Highlander, Ph.D., Partner, Intellectual Property, Fulbright & Jaworski LLP
5:45 End of Day
WEDNESDAY, JUNE 10
7:00 am - 4:00 pm Registration Open
7:00 - 8:00 am Facilitated Break-Out Discussion Groups and Continental Breakfast
8:15 Chairperson’s Remarks
Christophe J. Echeverri, Ph.D., Chief Executive Officer and Chief Scientific Officer, Cenix BioScience GmbH
8:20 Overview of Key Takeaways from Break-Out Discussions
Christophe J. Echeverri, Ph.D., Chief Executive Officer and Chief Scientific Officer, Cenix BioScience GmbH
8:50 Use of RNAi Screens with Physiologically Relevant Cell Models to Identify Novel Therapeutic Targets
Namjin Chung, Ph.D., Senior Research Investigator Applied Genomics, Bristol-Myers Squibb Co.
9:20 A High-Throughput Chemical Biology Approach to Identify Modulators of the Hypoxia Inducible Factor (HIF) Pathway
Marc Ferrer, Ph.D., Senior Research Fellow, Automated Biotechnology, Merck & Co., Inc.
The hypoxia-inducible factor (HIF) pathway is essential for cell survival under low oxygen and plays an important role in tumor cell homeostasis. To identify critical genes that modulate the HIF pathway, we implemented a comprehensive high-throughput screening approach that included genome-scale siRNA and small molecule screens under hypoxic conditions. Results from the primary screens were combined with data from gene expression and cell imaging-based follow-up assays used to measure HIF pathway activity and with network-based analysis to reveal unique insights into how the HIF pathway is regulated.
9:50 Networking Coffee Break Poster and Exhibit Viewing
10:45 Unlocking the Genome with Pooled shRNA Screens
David Davis, Ph.D., Scientist, Molecular Biology, Genentech Inc.
Genome-wide shRNA libraries are a revolutionary tool for reverse genetic screens. The ability to pool large numbers of independent constructs has been shown to be an efficient screening approach. We have applied this technology to identify novel regulators of oncogenic signaling pathways. The advantages and considerations in the application and deconvolution of pooled shRNA libraries will be presented.
11:15 Panel Discussion: How Far Have We Progressed with the Targets Identified from RNAi Screens?
12:15 pm Close of Morning Session
12:30 pm Presentation 1 (Opportunity Available) or Lunch on Your Own
1:00 Session Break
1:45 Chairperson’s Remarks
Albert B. Seymour, Ph.D., Director of Biological Profiling, Target Generation Unit, Biotherapeutics and Bioinnovation Center, Pfizer, Inc.
1:50 Cancer Target Identification and Validation by siRNA Library Screening
Xiaoyu Lin, Ph.D., Associate Research Investigator, siRNA therapeutics, Abbott Laboratories
siRNA library screens have provided a powerful tool to identify cancer targets and advance our understanding of the complex nature of cancer biology. I will review the data from our recent siRNA library screens in an effort to identify novel druggable cancer targets. I will use several targets identified in the library screen as examples to discuss a general procedure for target validation including on-target confirmation, signaling pathway exploration and in vivo validation.
2:20 Establishing a siRNA Pipeline: From in vivo Target Validation to Use as a RNA Therapeutic
Steven Bartz, Ph.D., Director, Lead Development, Sirna Therapeutics (A wholly owned subsidiary of Merck & Co.)
A process has been established to enable use of siRNAs for in vivo target validation through rapid testing of candidate targets. Targets validated using siRNAs in animal models proceed to populate a pipeline for development of RNA therapeutics. This target validation to clinical development process has generated large amounts of in vivo data that drives continued improvement in siRNA lead development.
2:50 Networking Refreshment Break (Last Chance for Poster and Exhibit Viewing)
3:30 A Framework for the Analysis of RNAi Phenotypes as Quantitative Traits
Kim Quon, Ph.D., Principal Scientist, Amgen Inc.
siRNA phenotypes are usually interpreted like genetic knockout experiments: a gene’s normal function is inferred from its knockdown phenotype. However, because individual siRNAs against a given gene have differing knockdown efficiencies, a spectrum of quantitative phenotypes is typically obtained. We propose that siRNAs should therefore be treated analogously to hypomorphic allelic series rather than to knockouts. Using such a framework, we have developed rigorous methods for inferring true gene function from siRNA data, treating phenotypes as quantitative traits. We show that such a framework can be critical for properly interpreting siRNA screening and validation experiments, particularly when cell viability is a critical phenotype of interest as for oncology targets.
4:00 High-Throughput RNAi Genetic Screens for Drug Discovery and Development
Attila A. Seyhan, Ph.D., Head of RNAi and Compound Delivery and Screens Systems Biology Technologies, Wyeth Research
We have employed RNAi-based gene function analysis which has been recognized as a powerful approach when combined with high-content screening involving different parameters for defining a specific target. Using HeLa cells as model, we have screened 280 known cell cycle and 280 randomly selected genes from a custom pooled druggable genome siRNA library, demonstrating the utility of integrating the liquid handling workstation automation format with the endpoint readout of gene knockdown by high content screening for RNAi genetic screens. From this pilot study, we now are now expanding the RNAi gene targeting scale of this concept to include a larger “druggable-genome” or “genome-wide” RNAi library screens in arrayed (synthetic siRNA or Lentiviral-shRNA) or pooled (Lentiviral-shRNA) formats.
4:30 Human Genetic Approaches to Target Discovery and Validation: Starting With the Clinical Endpoint of Interest
Albert B. Seymour, Ph.D., Director of Biological Profiling, Target Generation Unit, Biotherapeutics and Bioinnovation Center, Pfizer, Inc.
5:00 Panel Discussion: Identifying the Bottlenecks in Target Validation
5:30 Close of RNAi for Target Identification and Validation Conference