2008年6月8日(日)～11日(三) 美国．旧金山．Fairmont Hotel

RNA干扰现象

RNAi FOR TARGET VALIDATION
June 9-10

第1日 | 第2日

6月 10日 (二)

7:30am - 6:00 pm Registration Open

7:30 am Breakfast Workshop (Sponsorships Available)

8:15 Chairperson’s Remarks
Richard Klinghoffer, Ph.D., Research Fellow, Biology, Rosetta Inpharmatics/Merck & Co., Inc.

8:20 Lentivirus-Mediated RNAi Screens
Richard Klinghoffer, Ph.D., Research Fellow, Biology, Rosetta Inpharmatics/Merck & Co., Inc.
To expand our capacity to interrogate disease-related gene families and signaling cascades by RNAi screens, we have established methods to produce and screen large collections of shRNA-containing lentiviral vectors. We have now used our methods to efficiently generate a screening compatible library of ~14,000 individually arrayed vectors targeting the human druggable genome (approximately 5,000 genes). Screens designed to identify novel regulators of disease have been performed and will be presented.

8:50 Rapid Creation of RNAi Libraries Using shRNA Microarrays
Michael C. Bassik, Ph.D., Post-doctoral Fellow, Laboratory of Michael T. McManus, Department of Cellular and Molecular Pharmacology and Diabetes Center, Department of Microbiology and Immunology, University of California, San Francisco
RNAi has become a widely used and powerful tool for conducting genetic screens. Lentiviral shRNA delivery is most effective for stable gene disruption in diverse cell types, but currently available libraries are limited in a number of critical ways. To address some of these problems, we have developed a quick and efficient strategy to use microarray synthesis of complex shRNA pools in order to generate highly adaptable RNAi libraries. These libraries are inexpensive to create and maintain, can be easily changed to accommodate new vector design, and are less costly and cumbersome to use than standard arrayed libraries. Most importantly, this new strategy allows for much more comprehensive and effective gene targeting. We show here that we can couple the use of these libraries with sorting flow cytometry to identify and quantitate the potency of shRNAs against a number of targets, providing a significant improvement over current screening methods.

9:20 Rational Design Leads to More Potent RNA Interference Targeting Hepatitis B Virus
Anton P. McCaffrey, Ph.D., Assistant Professor, Department of Internal Medicine, University of Iowa
Previously, we conducted proof-of-principle experiments using RNAi to degrade HBV RNAs in mice, and reduce levels of viral proteins and replicated DNA genomes. Recently we expressed the short hairpin RNA (shRNA), HBVU6#2, in HBV transgenic mice. While this RNAi trigger resulted in substantial HBV knockdown in mice, it also resulted in acute toxicity due to competition with the endogenous microRNA machinery. Using rational approaches based on mechanistic insights, we have designed RNAi triggers that are much more potent than the trigger identified in our original screen.

9:50 Networking Coffee Break, Poster and Exhibit Viewing

Panel Discussion:

Intellectual Property Challenges around RNAi Technologies & Therapies

10:45 Due Diligence for RNAi; How Do You Look at the Patent Landscape
Rochelle K. Seide, Ph.D., Patent Consultant
An analysis of the patent landscape surrounding RNAi technology and products is of particular importance in avoiding patent infringement and in licensing and other deals, such as company and/or product acquisitions. The presentation will provide an overview on how to carry out the analysis, including what to look for and how to avoid pitfalls.

11:00 Strategies for IP Protection around RNAi Therapeutics
Steven Highlander, Ph.D., Partner, Intellectual Property, Fulbright & Jaworski, LLP
RNAi technologies present fairly predictable challenges when it comes to securing patent protection. I will review the basic requirements for patent protection and apply each requirement to real world examples of RNAi inventions at various stages of development. Options and strategies for dealing with current U.S. PTO and EP examination practices will be discussed.

11:15 A Short Primer on Compliance with the Written Description Requirement as Required by U.S Patent Law
Vineet Kohli, Assistant Patent Counsel, Patent Department-OGC, Merck & Co., Inc.
A brief primer on what constitutes conception and written description of an invention relative to RNAi and its compliance with the U.S Patent statutes embodied in Title 35. The topic will include a discussion on how to avoid the various pitfalls attendant issued patents in the RNAi field, the most common of which is a re-Examination, which can be costly.

11:30 Questions from the Audience

11:45 Keynote Presentation
Small RNAs as Markers, Effectors, and Targets of Genetic Change
Andrew Fire, Ph.D., Nobel Laureate and Professor, Departments of Pathology and Genetics, Stanford University School of Medicine
The “Small-RNA-ome” of a cell or tissue sample gives us a remarkable window
into ongoing processes of gene regulation that have biological, procedural, and clinical consequences. This talk will provide several examples in which we hope that Small-RNA-ome determina-tion combined with other analysis will contribute to understanding of (and control over) critical biological processes.