NEW APPROACHES FOR RNAi DELIVERY

2:00pm Chairperson’s Remarks
Dmitry Samarsky, Ph.D., Vice President, Technology Development, RXi Pharmaceuticals Corp.

2:10 Development and Optimization of Novel Therapeutic RNAi Platform
Dmitry Samarsky, Ph.D., Vice President, Technology Development, RXi Pharmaceuticals Corp.
The design of therapeutic RNAi triggers will be discussed. We will also illustrate nanotransporter delivery of RNAi compounds to mouse tissues and demonstrate silencing of SOD1 in an ALS model. Lastly, validation of RIP140 as a target for obesity will be described.

2:40 Development of siRNA Therapeutics: The Challenge of Delivery
Michael Templin, Ph.D., D.A.B.T., Senior Director, Pharmacology and Toxicology, Nastech Pharmaceutical Co.
Delivery represents a significant hurdle for development of therapeutic siRNAs. We have modified lipid structures to decreased toxicity, while maintaining in vivo efficacy. Peptide conjugates, in particular with Dicer siRNAs, demonstrate in vitro or local in vivo activity; peptide-siRNA nanoparticles improve systemic delivery. Alone or in combination with modified lipids, peptides increase the siRNA payload, enhance delivery efficiency, and have the potential for targeting.

3:10 Liver-Specific Knockdown Using SNALP-Formulated siRNAs to Study Pathways in Lipoprotein Secretion and Steatosis
Pieter Peeters, Ph.D., Head of Functional Genomics, Research & Early Development Unit, Johnson & Johnson Pharmaceutical Research & Development
As the application of RNA interference in vivo further develops, we are pursuing several promising technologies for systemic delivery. The goal of the current study was to evaluate the SNALP (“Stable Nucleic Acid Particles”) systemic RNAi delivery platform to knockdown genes encoding for key enzymes in triglyceride synthesis. SNALP-Formulated siRNAs were found to effectively knockdown mRNA levels by >90% in liver compared to a SNALP-Delivered scrambled siRNA control. The effect knock-down in liver was further investigated following a 3-week high-fat feeding challenge. The results demonstrated the efficient in vivo SNALP-mediated delivery of siRNA by systemic route and the utility of targeting novel targets to reduce fat storage in liver and improve hepatic steatosis.

3:40 Networking Refreshment Break in the Exhibit Hall

4:20 A Novel Treatment for Fibrosis – Site Specific Delivery of siRNA in Novel Carriers
Lei Yu, M.D., Ph.D., Director of Biomedical Research, Nitto Denko Technical Corp.
We present data on novel biodegradable delivery vehicles conjugated with specific targeting moieties as efficient carriers of siRNA for in vivo therapeutic applications. Novel lipopolymers and lipids conjugated with vitamin A can specifically target the vitamin A storage cells (stellate cells) of liver, pancreas and lungs and deliver siRNA specific to HSP47, resulting in significant reduction in collagen synthesis and reversal of fibrosis. The data clearly demonstrate two levels of specificity – carrier/vitamin A-mediated as well as siRNA related. Design and synthesis of novel delivery vehicles for in vivo targeting, their structure property studies and efficacy in mRNA silencing are also discussed.

4:50 Technology Watch Sponsored by
Dicer-substrate Oligonucleotides (DsiRNAs) as Therapeutic Leads
Bob D. Brown, Senior Vice President, Research, Dicerna Pharmaceuticals, Inc.
DsiRNAs are RNA duplexes greater than 25 bases in length and substrates for cleavage by the enzyme Dicer. DsiRNAs are capable of triggering potent and long lasting RNA interference effects. Bioinformatics and high-throughput screening are used by Dicerna Pharmaceuticals to identify the most effective DsiRNAs against therapeutic target genes. Chemical modification and nanoparticle formulations are being used to advance DsiRNA hits to preclinical leads.

5:20 Iron Oxide Nanoparticles as Imaging-Capable siRNA Delivery Agents
Zdravka Medarova, Ph.D., Instructor, Radiology, Massachusetts General Hospital
Super-Paramagnetic iron oxide nanoparticles have traditionally been utilized as contrast agents for magnetic resonance imaging. The study of their potential for the delivery of molecular therapy, however, is still in its infancy. Our research explores the value of super-paramagnetic iron oxides as delivery modules for small interfering RNA to target organs, with a focus on the feasibility of combining the imaging and delivery capabilities of these nanoparticles for the tracking of siRNA bioavailability.

5:50 Targeted Nanoparticles for Delivery of Oligonucleotide Drugs to Cancer and Leukemia
Robert J. Lee, Ph.D., Associate Professor of Pharmaceutics, Ohio State University
Improving delivery of siRNA is critical to its clinical application. Incorporation into nanoparticles conjugated to a targeting moiety has been shown to greatly enhance the efficiency and specificity of siRNA delivery. Our research is focused on design and development of these nanoparticles for in vivo delivery of siRNA for potential clinical application.

6:20 Moving from In Vitro to In Vivo RNAi
Kristin Wiederholt, Ph.D., Research Area Manager, RNAi & Gene Regulation, Invitrogen

6:30-8:00 Dinner Reception Hosted by
Invitrogen invites you to spend an evening with your colleagues and other prominent researchers. Located in the foyer, this reception is opened to registered RNAi for Therapeutic conference attendees only.