Wednesday, June 11
7:00 am - 4:00 pm Registration Open
7:00-8:00
Beyond Talking - Communicating Facilitated Break-out
Discussion Groups and
Morning Coffee
8:15 Chairperson’s Remarks
Cristina M. Rondinone, Ph.D., Director Research Metabolic Diseases, F. Hoffmann-La Roche Inc.
8:20 RNAi Therapeutics: Dream or Reality?
Cristina M. Rondinone, Ph.D., Director Research Metabolic Diseases, F. Hoffmann-La Roche Inc.
RNAi holds considerable promise as an approach to silence disease-causing genes, particularly those that encode so-called non-druggable targets. However, major challenges for using the RNAi platform still exist. Will new discoveries in the field of RNAi biochemistry coupled with technological breakthroughs permit the creation of effective RNAi reagents for therapeutic applications?
8:50 RNAi Applications to Assess Target Mechanism and Safety:
From In vitro to In vivo
Laurence Whiteley, Ph.D.,
Senior Director, Pfizer
This presentation will detail strategies and approaches to apply RNAi technologies to enhance the understanding of target biology. These discussions will include details of hypothesis driven siRNA screening activities as well as targeted in vivo delivery of siRNA and shRNA molecules.
9:20 Strategies for RNAi-Based Therapies for the Treatment of HIV Infection
John Rossi, Ph.D., Professor and Chair, Molecular Biology, Beckman Research Institute of the City of Hope
We have been exploiting two different but complementary RNAi-based approaches for the therapeutic treatment of HIV infection. The first uses promoter expressed RNAi triggers delivered to hematopoietic cells by lentiviral vector transduction. Our second strategy relies upon anti HIV envelope targeting aptamers to deliver siRNAs targeting HIV into HIV infected cells. This dual inhibitory approach can be used to multiplex siRNAs and aptamers for potent inhibition of HIV replication and spread.
9:50 Networking Coffee Break, Poster and Exhibit Viewing
10:45 RNAi as a Contraceptive
Zev Williams M.D., Ph.D., Clinical Fellow, Obstetrics and Gynecology and Reproductive Medicine, Brigham and Women’s Hospital, Harvard Medical School
We propose for the first time, the use of RNAi as a contraceptive. Knock-out experiments in mice have shown that without ZP3, a component of the Zona
Pellucida, the coat surrounding all mammalian eggs, the mice are infertile. We tested the ability of specifically designed siRNAs to block ZP3 synthesis. Since ZP3 is uniquely expressed in growing
oocytes, RNAi inhibiting
ZP3 represents a novel and exciting new approach for the development of a reversible, non-hormonal contraceptive without systemic effects.
11:15 miRNA-Based Therapeutics for Cancer
Michele A. Cleary, Ph.D. Associate Scientific Director, Rosetta Inpharmatics, LLC
We study the role of microRNAs in tumorigenesis with the goal of developing novel approaches to the treatment of cancer. One such family, the miR-34 family, functions in the p53 DNA damage checkpoint by regulating a network of cell cycle genes. Another, the miR-106b family, promotes cell cycle progression and targets select cell cycle genes. An update of our under-standing of these two gene families and their potential as cancer therapeutics will be presented.
11:45 Identification of Single-Strand Antisense RNA Motifs that Inhibit Gene Expression by a RISC Mechanism
Walt Lima, Ph.D., Director, Molecular and Structural Biology, Isis Pharmaceuticals Inc.
It is the antisense strand of the siRNA that triggers the destruction of the target mRNA by binding to the RISC endonuclease Ago2. Therefore, we asked if we could substitute an appropri-ately modified antisense strand for the RNA duplex, as single-strand RNAs (ssRNAs) offer the additional advantages of reduced molecular weight, complexity and cost of manufacture com-pared to RNA duplexes. We have identified chemically modified ssRNA motifs with improved nuclease stabilities and potencies that degrade the target RNA in an Ago2 dependant manner.
12:15 pm Close of Morning Session
12:30 Luncheon Technology Workshop
(Sponsorship Available) or Lunch on Your Own
1:45 Chairperson’s Remarks
Cristina M. Rondinone, Ph.D., Director Research Metabolic Diseases, Hoffmann-La Roche Inc.
1:50 Temporary Inhibition of p53 by siRNA for Prevention of Acute Renal Failure: From Concept to Clinical Trials
Elena Feinstein, M.D., Ph.D., Chief Scientific Officer, NA, Quark Pharmaceuticals Inc.
We have developed siRNA against p53 to be used as systemic therapy for prevention of acute kidney injury (AKI) in response to ischemia-reperfusion stress. Pre-clinical efficacy studies in several AKI models in rats showed excellent therapeutic potential of the proposed approach. Following accomplishment of successful safety pre-clinical program indicating a large or safety margin, the drug has entered Phase 1 clinical trials in humans.
2:20 Development of the New RNAi Therapeutics Platform
Dmitry Samarsky, Ph.D., Vice President, Technology Development, RXi Pharmaceuticals Corp.
RNAi compounds are readily formulated with nanotransporters and activity is obtained at relatively low doses. Parameters for the design of therapeutic synthetic RNAi and its delivery to the mouse liver and other tissues will be discussed. Data demonstrating the knock down of SOD1 in a mouse ALS model will be shown. Lastly, the RNAi validation of RIP140 as a target gene for obesity will be described.
2:50 microRNA Therapeutics in the Intervention of Cancer Signaling
Andreas G. Bader, Ph.D., Senior Scientist, Drug Discovery, Asuragen Inc.
Similar to conventional oncogenes and tumor suppressors, microRNAs
(miRNAs) represent a key intervention point in targeted cancer therapy. We have analyzed tumor tissues and have identified miRNAs that are downregulated or lost in cancer. Gene expression profiling reveals that these miRNAs directly or indirectly control the expression of bona fide oncogenes and tumor suppressors. A review of these targets complements our phenotypic studies and provides an explanation for the
anti-oncogenic activities of miRNAs. Therefore, restoring the expres-sion of miRNAs by “miRNA replacement therapy” might provide a therapeutic benefit to patients with cancer.
3:20 Networking Refreshment Break, Last Chance for Poster and Exhibit Viewing
4:00 Poster Awards in the Exhibit Hall
