第二届广州核酸国际论坛

2014年11月5-7日,广州,科学城翡翠皇冠假日酒店

议题介绍

    核酸治疗药物,经历三十年的沉浮,随着关键技术的相继突破和新技术的不断涌现,已成为第三大治疗药物。近一年,核酸药物公司的市值增长了几十甚至上千倍,在这核酸治疗时代来临的时刻,第二届广州核酸国际论坛(CNAF)将以核酸治疗为主题,云集20-25位国际顶级科学家和企业家,聚焦核酸药物前沿技术和最新进展,探讨全新核酸治疗模式。论坛旨在推动核酸治疗药物的发展,加强中国与国际的交流合作,促进中国核酸生物产业的进步,展望激动人心的核酸产业前景!

     本届论坛的演讲嘉宾囊括诺贝尔奖得主、世界百强药企的高级主管、世界顶级学府的著名教授、核酸制药上市公司的总裁、核酸治疗世界联盟主席等!

内容涵盖RNAi、microRNA、antisense、lncRNA、exon-skipping等核酸药物开发全过程:从基础研究到商业推广,从临床前开发到临床研究,分享世界首个核酸药物成功经验!

本届论坛的主旨演讲将由三位在核酸治疗领域极富盛名的专家担任:2006年诺贝尔生理学或医学奖得主Craig Mello教授,法国赛诺菲高级总监Ekkehard Leberer教授,以及美国Isis制药公司Brett Monia教授。Mello教授及其同事在1998年证明了双链RNA分子引起基因沉默的生物过程,这一机制被称为RNAi。RNAi的发现革新了功能基因组学的研究手段,并为核酸治疗领域注入了新的活力。Mello教授因此发现在2006年被授予诺贝尔奖。Ekkehard教授是COMPACT的创始理事之一,这一组织是一个囊括了大型制药公司、知名学术机构及生物科技公司在内的联盟,致力于为大分子治疗开发新型且先进的递送系统,其中也包括核酸药物。Monia博士是核酸分子应用于生物化学及治疗的领军人物之一,全球核酸治疗协会(Oligonucleotide Therapeutics Society,简称OTS)的当选主席。OTS是全球核酸治疗最知名的国际组织之一,旨在推动核酸药物的开发。

论坛议程
Wednesday, November 5, 2014
Registration  13:00-18:00
Session 1: Thursday, November 6, 2014
08:30-08:45 Opening & Introduction Li-He Zhang, PhD  Professor, Peking University, China

CNAF Scientific Council & Organizing Committee

08:45-08:50 Chair Muthiah Manoharan, PhD  Senior Vice President, Alnylam Pharmaceuticals, USA
08:50-09:35 Opening Keynote Craig Mello, PhD  Professor, University of Massachusetts Medical School, HHMI, 2006 Nobel Prize Winner, USA

Title:  RNA-guided genome defense and new frontiers in biotech and medicine

09:35-10:00 Plenary Matthew Porteus, MD, PhD  Professor, Stanford School of Medicine, CRISPR Therapeutics Founder, USA

Title: Genome editing using engineered nucleases

10:00-10:25 Plenary Judy Lieberman, MD, PhD  Professor, Program Chair, Harvard Medical School, USA

Title: Targeted gene knockdown to treat cancer

10:25-10:45 Tea Break
10:45-11:25 Keynote Brett Monia, PhD  Senior Vice President, Isis Pharmaceuticals, OTS President, USA

Title: Transforming drug discovery for human therapeutics with antisense technology

11:25-11:50 Plenary Erwei Song, MD, PhD  Professor and Vice Dean, Sun Yat-Sen Memorial Hospital, China

Title: BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10

11:50-12:00 Technology Richard Hogrefe, PhD  Founder, President and Chief Executive Officer, TriLink BioTechnologies, USA

Title: Designing a mRNA therapeutic suitable for scale up

12:00-13:30 Lunch
13:30-13:35 Chair Brett Monia, PhD  Senior Vice President, Isis Pharmaceuticals, OTS President, USA
13:35-14:15 Keynote Troels Koch, PhD  Senior Vice President and Chief Technology Officer, Santaris / Roche, Denmark

Title: LNA antisense – concepts & status

14:15-14:40 Plenary Georg Sczakiel, PhD  Professor, University of Lübeck, Germany

Title: Target RNA is involved in guide strand loading of Argonaute-2 and siRNA-induced RNA interference

14:40-15:05 Plenary Linfeng Huang, PhD  Assistant Professor, City University of Hong Kong, China

Title: Bacteria as siRNA factory

15:05-15:25 Tea Break
15:25-15:50 Plenary Chen-Yu Zhang, MD, PhD  Professor and Dean, School of Life Sciences,Nanjing University,China

Title: Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses

15:50-16:15 Plenary Peixuan Guo, PhD  Professor, William S. Farish Fund Endowed Chair, University of Kentucky, USA

Title: A new generation of drugs from the emerging field of RNA nanotechnology

16:15-16:25 Technology Suresh Srivastava, PhD  Founder and President, ChemGenes, USA

Title: BMEG oligonucleotides for efficient cellular delivery for therapeutic and molecular biological applications

16:25-16:50 Plenary David Lewis, PhD  Chief Scientific Officer, Arrowhead Research Corporation, USA

Title: Using Dynamic Polyconjugate® technology to advance RNAi-based therapeutics

16:50-17:00 Day End

Remarks

CNAF Organizing Committee
Session 2: Friday, November 7, 2014
09:00-09:05 Chair Troels Koch, PhD  Senior Vice President and Chief Technology Officer, Santaris / Roche, Denmark
09:05-09:45 Keynote Ekkehard Leberer, PhD  Professor, Senior Director of R&D Alliance Management, Sanofi, Germany

Title: Nucleic acid therapeutics: opportunities and challenges for innovation in drug development

09:45-10:10 Plenary William Marshall, PhD  President and Chief Executive Officer, Board Director, miRagen Therapeutics, USA

Title: Discovery and development of microRNA targeting therapeutics

10:10-10:35 Plenary Micky Tortorella, PhD  Chief Technology Officer and Vice President for Drug Discovery and Technology Transfer, Guangzhou Institutes of Biomedicine and Health, China

Title: Intra-articular delivery of siRNA-conjugates as new disease modifying osteoarthritis drugs

10:35-10:55 Tea Break
10:55-11:20 Plenary Chengyu Jiang, PhD  Professor, Chair, Peking Union Medical College, CAMS, China

Title: Hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p inhibitors can reduce the cytotoxicity of Ebola virus glycoprotein in vitro

11:20-11:45 Plenary Marc Lemaitre, PhD  Chief Executive Officer, Sirnaomics, USA / China

Title: Improving siRNA therapeutics using polymer-nanoparticle (PNP) delivery: recent pre-clinical results with STP705 against skin scars

11:45-12:00 Technology Kimo Sanderson  Vice President, Asahi Kasei, Japan

Title: Therapeutic oligonucleotides from discovery to development: the importance of proper production and scale up

12:00-13:30 Lunch
13:30-13:35 Chair William Marshall, PhD  President, Chief Executive Officer, Board Director, miRagen Therapeutics, USA
13:35-14:15 Keynote Muthiah Manoharan, PhD  Senior Vice President, Alnylam Pharmaceuticals, USA

Title: Chemical strategies for systemic delivery of RNAi drugs

14:15-14:40 Plenary Dirk Haussecker, PhD  Founder and Curator, RNAi Therapeutics Blog, Germany

Title: RNA therapeutics emerging as major drug discovery engine

14:40-15:05 Plenary Sven Klussmann, PhD  Chief Scientific Officer, NOXXON Pharma, Germany

Title: From bench to bedside – the conversion of mirror-image oligonucleotides into therapeutics

15:05-15:15 Technology Carina Andersson, PhD  Marketing Head, GE, USA

Title: A manufacturing solution of oligonucleotides

15:15-15:35 Tea Break
15:35-16:00 Plenary Ryszard Kole, PhD  Distinguished Scientist, Professor, Sarepta Therapeutics, USA

Title: Eteplirsen, a phosphorodiamidate morpholino oligonucleotide, as treatment for Duchenne muscular dystrophy

16:00-16:25 Plenary Yi Jin, PhD  Executive Vice President, Suzhou Ribo Life Science, China

Title: RNAi based therapeutics for Hepatitis B

16:25-16:50 Plenary René Thürmer, PhD  Deputy Head of the Unit Pharmaceutical Biotechnology, BfArM – Federal Institute for Drugs and Medical Devices, Germany

Title: Regulatory aspects of nucleic acids therapeutics

16:50-17:00 Closing Remarks Craig Mello, PhD  Professor, University of Massachusetts Medical School, HHMI, 2006 Nobel Prize Winner, USA

CNAF Scientific Council & Organizing Committee

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合作媒体

演讲嘉宾

郭培宣博士

William S. Farish 纳米生物技术首席讲座教授

美国肯塔基大学纳米生物技术中心主任

美国国家癌症研究所(NCI)癌症纳米技术平台合作计划主任

Dr. Guo received his Ph.D. in Microbiology and Genetics with training in biophysics from the University of Minnesota in 1987. He was a postdoc at NIH before joining Purdue University as an assistant professor in 1990, tenured in 1993, full Professor in 1997, and was honored as a Purdue Faculty Scholar in 1998. He founded two Interdisciplinary Graduate Programs and established a NIH Nanomedicine Development Center at Purdue.   He was recruited to University of Cincinnati as the Dane & Mary Louise Miller Endowed Chair of Biomedical Engineering in 2007, and was Director of the NIH Nanomedicine Development Center relocated from Purdue to University of Cincinnati.

He constructed the first viral DNA packaging motor in vitro (PNAS, 1986), discovered phi29 motor pRNA (Science, 1987), assembled infectious dsDNA viruses (J Virology, 1995), discovered pRNA hexamer (Mol Cell, 1998, featured in Cell), and pioneered RNA nanotechnology (Mol Cell, 1998, JNN, 2003; Nano Letter., 2004, 2005; Nature Nanotechnology 2010, 2011). His lab built a dual imaging system to detect single-fluorophores (EMBO J, 2007; RNA, 2007), incorporated the phi29 motor channel into a lipid membrane (Nature Nanotechnology, 2009) for single molecule sensing with potentials for high throughput dsDNA sequencing. Recently, his lab discovered a third class of biomotor using revolution mechanism without rotation.

He received the Pfizer Distinguished Faculty Award in 1995; the Purdue Faculty Scholar award in 1998; the Purdue Seed Award in 2004, 2005, and 2007; the Lions Club Cancer Research Award in 2006; and COV Distinguished Alumni of the University of Minnesota in 2009, and many other awards for research excellence. He is an editor or board member of five nanotech journals. His work has been reported hundreds of times over the radio or TV such as ABC and NBC, and featured in Newsletters or websites of NIH, NSF, MSNBC, NCI and ScienceNow etc. He was a member of two prominent national nanotech initiatives sponsored by NIST, NIH, NSF and National Council of Nanotechnology; director of one NIH Nanomedicine Development Center from 2006 to 2011; member of the NIH NDC Steering Committee from 2006-2010; NIH/NCI intramural site-visit Review Panel at 2010 and 2014; Panelist for DOD-US Army, Navy & Air Force Joined Medical Program in 2003; member of the Examination and Review Panel (Oversee Expert) of the Chinese Academy of Sciences since 2014.

Presentation Title

A New Generation of Drugs from the Emerging Field of RNA Nanotechnology

Summary

RNA has recently emerged as an important nanotechnology platform due to its diversity and versatility in structure and function. RNA nanoparticles can be fabricated with a level of simplicity characteristic of DNA, while possessing an adaptable tertiary structure and catalytic functions that can mimic some forms of proteins. RNA is unique in comparison to DNA by virtue of its higher thermodynamic stability, ability to form both canonical and noncanonical base pairings, capability in base stacking, and distinctive in vivo attributes. RNA nanotechnology involves bottom-up approaches to assemble nanometer scale particles with its main constituent composed of RNA.

We have constructed an assortment of thermodynamically and chemically stable RNA nanoparticles that carry multiple therapeutics. These nanoparticles self-assemble very efficiently, are resistant to boiling, RNase and 8M urea denaturation, and remain intact after injection into the body. Each arm of the RNA helices can harbor one siRNA, miRNA, ribozyme, or aptamer without affecting the folding of the RNA core, nor that of each daughter therapeutic RNA molecule. Gene silencing effects have been found to progressively enhance as the number of siRNA in each pRNA nanoparticle has been gradually increased. More importantly, systemic injection for bio distribution assay of the ligand-containing nanoparticles into the tail-vein of mice has revealed that the RNA nanoparticles remained intact without showing any signs of dissociation or degradation; and strongly bound to cancers without accumulation in other organs or tissues. Pharmacokinetic analysis has revealed that its half-life has been extended 10-fold, as compared to the siRNA counterpart. Particles tested in vivo have revealed that they did not induce cytokines, interferon-I, antibody, and toxicity; and retained favorable pharmacokinetics profiles.

Further reading:

1. Jasinski DL, et al. and Guo P. Physicochemically tunable poly-functionalized RNA square architecture with fluorogenic and ribozymatic properties. ACS Nano. 2014 (In Press).

2. Khisamutdinov E, et al. and Guo P. Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles. Nucleic Acids Research. 2014 (In press).

3. Khisamutdinov E, et al. and Guo P. RNA as a Boiling-Resistant Anionic Polymer Material To Build Robust Structures with Defined Shape and Stoichiometry. ACS Nano. 2014. 8: 4771

4. Shu Y, et al. and Guo P. Fabrication of pRNA nanoparticles to deliver therapeutics. Nature Protocol. 2013. 8:1635.

5. Shu Y, et al. and Guo P. Fabrication of 14 different RNA nanoparticles for specific tumor targeting without accumulation in normal organs. RNA. 2013.19:767.

6. Haque F, et al. and Guo P. Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers. Nano Today. 2012. 7:245.

7. Shu D, et al. and Guo P. Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics. Nature Nanotech. 2011. 6:658.

8. Abdelmawla S, et al. Guo P and Li QX. Pharmacological characterization of chemically synthesized monomeric phi29 pRNA nanoparticles for systemic delivery. Molecular Therapy. 2011. 19:1312.

9. Guo P. The emerging field of RNA nanotechnology. Nature Nanotech. 2010. 5: 833.

10. Guo, P. et al. Inter-RNA Interaction of phage phi29 pRNA to Form a Hexameric Complex for DNA Transportation. Mol. Cell. 1998. 2:149 (first paper to prove of concept of RNA Nanotechnology, feature in Cell).

Dirk HAUSSECKER 博士

RNA 治疗领域专家及咨询顾问,国际知名博客 RNAi Therapeutics 创建者及运营者

Dirk Haussecker is an expert and independent analyst of the RNA Therapeutics industry, with 12+ years of closely following the field.  He received his training in molecular biology of RNA processing and RNAi gene silencing at Edinburgh University, Scotland (Bachelor of Science, Honors 2000-2002), Oxford University, England (Doctoral degree, 2002-5), and Stanford University, USA (Post-doctoral studies, USA, 2005-2009), before fully focusing on the interplay between the science and business of RNA Therapeutics.  Dr. Haussecker has advised numerous biotechnology companies on business development matters and strategic directions.  He also helps investors to understand the underlying technologies and offers insights into the dynamics of the industry.  He provides insightful coverage of the RNA therapeutics field in his widely followed and highly regarded blog www.RNAiTherapeutics.blogspot.com [中国访客请点此阅读本博客文章], which he created and manages for the past nearly 10 years.

  1. RNAi Efforts Ready to Pay Dividends (2011) Genetic Engineering News (link)
  2. The Business of RNAi Therapeutics (2012) Molecular Therapy Nucleic Acids (link)

Presentation Title

RNA Therapeutics Emerging as Major Drug Discovery Engine

Summary

RNA Therapeutics is an area of drug development that comprises a number of nucleic acid-based modalities including gene silencing by RNAi and antisense, the modulation of RNA processing, and messenger RNAs for protein expression.  The combination of increased technological maturity and the explosion in the insight into disease genetics has allowed this sector to rapidly emerge as the 3rd major drug discovery engine in the pharmaceutical industry following small molecules and recombinant proteins.  This presentation will discuss the promise of RNA Therapeutics, recent technological and clinical progress, and then provide an outlook on how the RNA Therapeutics revolution will likely unfold over the next 3-4 years.  Some of these developments including in HBV infection and liver cancer will directly touch on diseases of high medical priority in China.

Linfeng HUANG (黄林峰) 博士

香港城市大学生物医学系助理教授

Dr. Linfeng Huang is an Assistant Professor at the Department of Biomedical Sciences, City University of Hong Kong. Dr. Huang received his BSc degree in Biological Sciences at China Agricultural University in Beijing. He did his PhD study with Prof. Sir David Baulcombe at the Sainsbury Laboratory in UK. He then did his postdoctoral training with Prof. Judy Lieberman at Boston Children’s Hospital and Harvard Medical School in USA before joining CityU in 2014. Dr. Huang has made a few significant discoveries in the RNAi field. During his PhD, he discovered the subunit structure and associated regulatory factors of a novel DNA-dependent RNA polymerase complex, Pol V, which is essential for transcriptional gene silencing in plants. More recently he discovered a species of bacterial small RNAs which is similar to eukaryotic siRNAs. Those bacterial siRNA-like small RNAs, named pro-siRNAs (for prokaryotic siRNAs), were stabilized by ectopic expression of a plant viral siRNA binding protein, p19. Based on this discovery, he co-invented, with Prof. Judy Lieberman, a technology of producing gene specific ‘recombinant’ siRNAs in bacteria.

Presentation Title

Bacteria as siRNA factory

Summary

We invented a method of making siRNAs directly from bacterial cells. This method utilizes p19 siRNA binding protein, found in a plant RNA virus, which stabilizes a cryptic bacterial siRNA-like RNA species (named pro-siRNAs for prokaryotic siRNAs). pro-siRNAs can be engineered to target any gene and are as effective as synthetic siRNAs without immunogenicity or off-target effect. Furthermore pro-siRNAs, as a pool of multiple siRNAs targeting the same gene, could be particularly suitable for suppressing more variable viral and oncogenic genes. We envision pro-siRNA could become a valuable and cost-effective tool for a wide range of RNAi applications. 

Chengyu JIANG (蒋澄宇) 博士

中国医学科学院基础医学研究所,生物化学与分子生物学系主任、教授

Chengyu Jiang is a professor and head of Department of Biochemistry and Molecular Biology, Peking Union Medical College (PUMC) and Chinese Academy of Medical Sciences. She obtained her PhD from Brown University in 1997 and followed by postdoctoral training at Massachusetts General Hospital, affiliated to Harvard Medical School before joining PUMC in 2003. Her research is to elucidate molecular pathogenesis of RNA viruses such as SARS-CoV, Avian Flu H5N1, S-OIV-H1N1, and Ebola, as well as to explore the molecular pathogenesis of acute lung injury induced by nanoparticles. Dr. Jiang has published extensively in numerous peer reviewed journals including Nature, Nature Medicine, Cell, and science signaling. She is also an inventor of a number of international patents. Some of the patents are exclusively licensed to a top 5 international pharmaceutical company and an international biotech company. She has served as member of WHO IARC fellowship committee in Lyon, France from 2005 to 2008 and as the chair in the year of 2007/2008. She received numerous honors including “Cheung Kong” Scholar, the young woman scientist of China, and national outstanding young award fund.

Presentation Title

Hsa-miR-1246, Hsa-miR-320a and Hsa-miR-196b-5p Inhibitors Can Reduce The Cytotoxicity of Ebola Virus Glycoprotein In Vitro

Summary

Ebola virus (EBOV) causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91% in Zaire, the most lethal strain. Though the viral envelope glycoprotein (GP) mediates widespread inflammation and cellular damage, these changes have mainly focused on alterations at the protein level, the role of microRNAs in the molecular pathogenesis underlying this lethal disease is not fully understood. Here, we reported that the microRNAs (miRNAs) hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p were induced in human umbilical vein endothelial cells (HUVECs) following expression of EBOV GP. Among the proteins encoded by predicted targets of these miRNAs, the adhesion-related molecules tissue factor pathway inhibitor (TFPI), Dystroglycan1 (DAG1) and the Caspase 8 and FADD-like apoptosis regulator (CFLAR) were significantly downregulated in EBOV GP-expressing HUVECs. Moreover, inhibition of hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p, or overexpression of TFPI, DAG1 and CFLAR rescued the cell viability that was induced by EBOV GP. Our results provide a novel molecular basis for EBOV pathogenesis and may contribute to the development of strategies to protect against future EBOV pandemics.

金毅博士

苏州瑞博生物技术有限公司执行副总裁

Dr. Yi Jin joined Suzhou Ribo Life Science as executive vice president in early of 2013 with more than 15 years of industry experience in oligonucleotide therapeutics, polymer anticancer nanomedicine, and antiviral drug discovery and development. Prior to joining the Company, She worked as a director in Nitto Denko Technical Corporation/Kinovate Life Science (Oceanside, CA), leading NittoPhase/NittoPhaseHL Solid Support R&D and commercialization, siRNA CMC,  siRNA Drug Delivery technology development, siRNA Drug development, and polymer-based anticancer drug R&D. She also worked with increasing responsibility at NovoPharm Biotechnology Inc. (Winnipeg, Canada), Origenix Technologies Inc. (Quebec, Canada), Biota Inc. (Carlsbad, CA), and ISIS Pharmaceuticals Inc. (Carlsbad, CA). Her academic training includes Ph.D. in nucleic acid chemistry at McGill University (Montreal, Canada), B.Sc. in Chemistry and M.Sc. in Organic Chemistry from Sun Yat-Sen University (Guangzhou, China).

Presentation Title

RNAi based therapeutics for Hepatitis B

Summary

There are 350 – 400 million people worldwide chronically infected with hepatitis B virus (HBV) annually. Current drugs are not satisfactory for all patients and it is impossible to reach the purpose of functional cure. RNAi technique makes it possible to suppress both viral antigen and DNA replication via silencing viral mRNAs.  In present study, anti-HBV X gene siRNAs were designed and selected. Candidate siRNAs with chemical modifications were stable up to 72 hrs in 90% human plasma and were able to attenuate the off-target effect caused by unmodified siRNAs. One leading siRNA was encapsulated within liver-targeting LNP delivery system RBP131 to form RB-HBV008 complex. The delivery system RBP131 was demonstrated high efficacy (ED50=0.05mg/kg). Neither hepatic and renal toxicity nor immunostimulation was observed at 24 and 48 hrs postinjection in mice. In various HBV mouse models, RB-HBV008 robustly suppressed HBV mRNA expression with a KD efficiency >90% post administration. RB-HBV008 dose-dependently reduced not only the levels of HBV DNA replication but also HBsAg and HBeAg with long duration. Specific mRNA cleavage was demonstrated both in vitro and in vivo via RACE PCR analysis. We concluded that RB-HBV008 is able to significantly suppress both viral antigens and DNA replication by siRNA cleavage of HBV mRNA, leading to HBV antigen seroconversion and potential functional cure in clinical.

Sven KLUSSMANN 博士

德国NOXXON制药公司首席科学家

Sven Klussmann, NOXXON’s Chief Scientific Officer, is co-founder of NOXXON Pharma AG. At the Free University Berlin, Dr Klussmann was the first person to demonstrate the principles of Spiegelmer Technology. He transferred the Spiegelmer discovery process from an academic environment into a robust, therapeutic-lead generating process. During this time he has authored more than 70 articles and over 40 patents on oligonucleotides and their applications.

Dr Klussmann was significantly involved in acquiring more than 100m EUR venture capital from blue-chip investors and closing collaborations with Pharma companies. From 2006 to 2008, Dr Klussmann served NOXXON in a twofold function as Chief Scientific and Chief Executive Officer. In this dual role he initiated NOXXON’s transformation from a technology-focused drug discovery company into an innovation-driven drug development organization. As a result, three drug candidates have successfully passed Phase I studies and are now tested in patients in four different Phase II clinical trials.

Presentation Title

From bench to bedside – The conversion of mirror-image oligonucleotides into therapeutics

Summary

On the basis of an in vitro evolutionary process, mirror-image RNA or DNA oligonucleotides can be identified to bind and inhibit pharmacologically relevant target molecules conceptually similar to monoclonal antibodies. Such molecules are termed L-aptamers or Spiegelmers. Several Spiegelmer against a variety of targets have been identified. Currently, three Spiegelmer-based compounds are evaluated in clinical studies. So far, Spiegelmers have been shown to be safe and well tolerated. Moreover, strong signs of efficacy in patients have been reported. The identification of a Spiegelmer candidate and its preclinical and early clinical characterization will be presented.

Troels KOCH 博士

丹麦Santaris制药公司首席技术官,研发副总裁

Dr. Troels Koch (TK) is Ph.D. in bio-organic chemistry and has worked in the area of nucleic acid chemistry and biology for more than 15 years. TK is co-founder of several Biotech companies of which Exiqon A/S and Santaris Pharma A/S are most commonly known. He is presently Vice President of Research & CTO in Santaris Pharma A/S with main responsibilities to further build on the fundamental understanding of the chemical and biological properties of LNA, refining the LNA antisense drug discovery process, and establishing a drug pipeline on RNA antagonists targeting both mRNA and microRNA. Collectively this work and associated IP has been a driver behind the four major partner deals that Santaris has entered over the past years. During his academic and biotech career TK has gained experience in managing R & D activities, intellectual property, quality systems, regulatory affairs, antisense drug substance/product manufacturing, and nucleic acid bio-organic chemistry. TK is the author of about 70 peer reviewed scientific papers and inventor of about 25 base patents. He is a frequently invited speaker at international conferences, and he has accepted more than 70 invitations in the past decade.

Presentation Title

LNA Antisense–Concepts & Status

Summary

Highlights for therapeutic LNAs will be presented with a focus on recent progress.  The contemporary trends in the field of oligonucleotides will influence future developments and it will be discussed how improvements may benefit from taking a fresh view and reconsider older concepts.

Ryszard KOLE 博士

美国Sarepta公司杰出科学家

Dr. Kole is a pioneer in the use of oligonucleotides for modulation of splicing and exon skipping and one of the leaders in the field of mRNA processing. He is currently a Distinguished Scientist at Sarepta Therapeutics, previously AVI BioPharma, the company he joined in 2008 as SVP Discovery Research. Prior to AVI he was Professor of Pharmacology at the University of North Carolina at Chapel Hill where he invented oligonucleotide-induced pre-mRNA exon skipping and founded Ercole Biotech. Ercole’s technology is now being developed by Sarepta, which acquired Ercole, for treatment of Duchenne muscular dystrophy (DMD) and other disorders. Dr. Kole authored and co-authored over 100 scientific publications and is a member of several editorial and scientific advisory boards. Dr. Kole received his postdoctoral training in biology and genetics at Yale University and his Ph.D. degree in chemistry at the Institute of Biochemistry and Biophysics, Warsaw Poland.

Presentation Title

Eteplirsen, a phosphorodiamidate morpholino oligonucleotide, as treatment for Duchenne muscular dystrophy (DMD).

Summary

Eteplirsen induces skipping of exon 51 in dystrophin pre-mRNA in the muscles of DMD patients treated with the drug. This treatment restores the reading frame of the defective dystrophin mRNA, leading to translation of functional dystrophin protein. Efficacy of eteplirsen was demonstrated in key clinical measures such as six-minute walk test and pulmonary function test. Importantly, the drug was well tolerated throughout the trial and there were no significant treatment-related adverse events. The results of the continuing trial after 120 weeks of treatment will be presented.

Ekkehard LEBERER 博士, 生物化学教授

法国赛诺菲高级总监

IMI COMPACT Consortium 创会理事

Dr. Leberer received his Ph.D. in Biology at the University of Konstanz, Germany (1986). He conducted post-doctoral training in molecular biology at the Banting and Best Institute of the University of Toronto, Canada, and then became a Professor of Biochemistry at the University of Konstanz, Germany (1992). He is currently responsible for R&D Alliance Management at Sanofi, and is the Scientific Managing Director of the Innovative Medicine Initiative COMPACT Consortium on the delivery of biopharmaceuticals across biological barriers and cellular membranes (www.compact-research.org).

Since joining Hoechst Marion Roussel in 1998, Dr. Leberer carried out various managing roles in this company, Sanofi’s predecessor companies and Sanofi itself, including responsibilities in functional genomics, biological sciences and external innovation for oligonucleotide-based therapeutics. He has also served as Head of Biotechnology Germany and a member of the Scientific Review Committee of Aventis Pharma Germany.

Prior to joining pharmaceutical industry, Dr. Leberer served as Senior Research Officer in genetics and genomics at the Biotechnology Research Institute, National Research Council of Canada, Montreal. His research has focused on the molecular mechanisms of signal transduction and the role of signalling molecules in human diseases. He is the principal discoverer of the p21 activated protein kinase (PAK) family of cell signalling proteins and of novel virulence-inducing genes in pathogenic fungi. He is co-author of more than 60 publications in prestigious peer-reviewed journals including Nature and Science.

Presentation Title

Nucleic acid therapeutics: Opportunities and challenges for innovation in drug development

Summary

Oligonucleotides such as siRNAs, antimiRs, miRNA mimics, lncRNAs and antisense oligonucleotides offer unique opportunities for developing novel therapeutic modalities against disease-relevant targets by rational drug design instead of random screening for small molecule modulators. Moreover, miRNAs open a novel target space by modulation of disease relevant miRNA-regulated biochemical pathways and networks of pathways instead of modulation of single targets. However, a key hurdle for translating oligonucleotide-based therapeutics into clinical applications remains their effective delivery across biological barriers and cellular membranes in order to reach their disease-relevant targets in the patient.

This presentation will summarize the opportunities of oligonucleotide-based therapeutics for innovation in the pharmaceutical industry, illustrate the major hurdles for translating these therapeutic modalities into the clinic, and describe examples of concepts that pharmaceutical companies are employing to overcome these hurdles.

Marc LEMAITRE, PhD

Chief Executive Officer, Sirnaomics, USA

Marc holds a degree in Organic Chemistry and a PhD in Biochemistry from the University of Liège, Belgium.  Since 1980 the “fil rouge” of Marc’s professional interests has been the study of the Nucleic Acids. After pioneering work on Antisense and oligo delivery in Montpellier, France, followed by 2 years in the lab of Nobel Prize winner Dr. Montagnier at the Pasteur Institute in Paris, Marc held positions of increasing seniority in R&D, operations, business development, and general management within CMO’s, Pharma and Biotech companies.  He moved to the USA in 2006 in a leadership role with Glen Research, before being recruited in 2009 as CEO of Girindus America, a CMO with a focus on the cGMP manufacture of oligonucleotides for therapeutic applications. In this role, Marc also held the legal responsibility of President of the management board of the German listed company Girindus AG, adding invaluable experience of leadership of a public company.

Having negotiated the merger between Nitto-Denko Avecia and the US operations of Girindus, Marc agreed to stay for a year to facilitate the integration of the newly merged entities. He joined Sirnaomics in 2014 as CEO of Sirnaomics, Inc.

Presentation Title

Improving siRNA therapeutics using Polymer-Nanoparticle (PNP) Delivery: Recent Pre-clinical results with STP705 against Skin Scars.

Summary

Small interfering RNA (siRNA) has outstanding potential as a therapeutic agent. Several contributions to improvements in their tissue and cellular delivery has thus far been made with a variety of encapsulating structures, large terminal conjugates and cell surface receptor ligands. Sirnaomics is developing specific PNP systems for siRNA delivery, both locally and/or systemically.  This PNP technology allows selection of the best approach to ensure efficient and safe delivery of siRNAs to their target tissues. Three generations of nanoparticle systems for siRNA delivery are being developed.

Our first generation of delivery agents uses clinically viable nanoparticles. Biodegradable Histidine-Lysine copolymer (HKP) is the proprietary delivery system for our leading siRNA therapeutic candidate [STP705]. It self-assembles with siRNA into nanoparticles having average size of 150 nM in diameter. In this presentation, we will show and discuss new data and results related to the CMC, formulation and animal toxicity profile of the STP-705 drug product.  We will also show how that PNP can significantly enhance therapeutic activity of the siRNAs without compromising safety of patients.

David LEWIS 博士

美国Arrowhead研究公司首席科学家

David Lewis, PhD, is the Chief Scientific Officer at Arrowhead Research Corporation, a development stage biotechnology company specializing in RNAi-based therapeutics. Dr. Lewis was a pioneer in the use of RNAi in animals and was the first to show that siRNAs could be used to inhibit gene expression in multiple tissues of adult mammals. He is a co-inventor of Dynamic PolyConjugate (DPC) technology for targeted delivery of siRNA, which is currently in clinical development for the treatment of chronic hepatitis B viral infection. Prior to his role at Arrowhead, Dr. Lewis was Site Head and Director of RNA Therapeutics at Roche’s research and development facility in Madison, WI.

Dr. Lewis received his BS degree in Biochemistry and Molecular Biology from the University of Wisconsin and his PhD in Biochemistry from Michigan State University. His post-doctoral studies were performed at the Howard Hughes Medical Institute at the University of Wisconsin. Dr. Lewis has authored more than 25 scientific papers and book chapters, and is co-inventor on over 25 patents and patent applications. He has served on several NIH review panels and is a lecturer in the Masters in Biotechnology Program at the University of Wisconsin.

Presentation Title

Using DPC technology to advance RNAi-based therapeutics

Summary

We have developed a targeted, polymer-based siRNA delivery platform called Dynamic Polyconjugate (DPC). Keys to this technology are an endosomolytic polymer and an environmentally sensitive polymer masking chemistry. The masking chemistry prevents the polymer from interacting with blood components and other non-targeted tissues, but is reversible in the acidic environment of endosomes allowing activation of the polymer and siRNA release to the cytoplasm. We are currently utilizing hepatocyte-targeted DPCs in clinical trials for the treatment of chronic Hepatitis B virus infection.

Judy LIEBERMAN, MD, PhD

Chair in Cellular and Molecular Medicine, Boston Children’s Hospital and Professor of Pediatrics, Harvard Medical School, USA

Judy Lieberman earned a Ph.D. in physics from Rockefeller University, worked as a theoretical physicist at the Institute for Advanced Study in Princeton and Fermilab, received an M.D. from Harvard and MIT, and trained in hematology-oncology at Tufts Medical Center and as a postdoctoral fellow at the Center for Cancer Research at MIT. She worked as a hematologist-oncologist at Tufts before moving to Harvard Medical School in 1995. At Harvard Medical School she served as Director of the Division of AIDS from 2005 to 2009 and is currently the Chair of the Executive Committee on Immunology. She is a member of the American Academy of Arts and Sciences.

The Lieberman laboratory has been in the forefront of developing RNAi-based therapeutics and using RNAi for genome-wide screening. They were the first to demonstrate that siRNAs could protect mice from disease. They developed methods to harness RNAi to inhibit herpes and HIV transmission in animal models and are developing strategies for cell-targeted RNAi to treat viral infection, immune disease and cancer. They also study the role of microRNAs in cancer. The Lieberman laboratory also studies how killer lymphocytes protect us against infection and cancer.

Presentation Title

Targeted gene knockdown to treat cancer

Summary

The major obstacle to harnessing RNAi for treating cancer is delivering RNAs into disseminated cancer cells. Aptamer-siRNA chimeras (AsiC) are a flexible and effective RNA delivery platform to accomplish this goal. RNA aptamers, structured RNAs that bind with high affinity to a protein, covalently linked to siRNAs, cause knockdown selectively in cells bearing the receptor the aptamer recognizes. Dr. Lieberman will discuss AsiCs that target a receptor highly expressed on epithelial cancer cells and on the tumor-initiating cells (also known as cancer stem cells) within them. Tumor cells selectively take up these RNAs, resulting in rapid and complete regression of difficult-to-treat aggressive breast cancer xenografts. These RNAs also target breast cancer stem cells and block their ability to initiate tumors. These results suggest that tumor-targeting AsiCs could be used to treat epithelial breast tumors and the T-ICs within them, sparing normal cells.

Muthiah (Mano) MANOHARAN 博士

美国Alnylam制药公司高级副总裁,新药开发负责人

Oligonucleotide Therapeutics Society 董事会成员

Muthiah Manoharan earned his PhD in Chemistry at the University of North Carolina, Chapel Hill. He did post-doctoral research on DNA repair enzymes at Yale University and the University of Maryland with Prof. John Gerlt. He has been an oligonucleotide chemist since 1983 and became involved in oligonucleotide-based therapeutics at Lifecodes (Valhalla, New York), during the early days of antisense research. He moved to Isis Pharmaceuticals in 1990, and contributed to company’s growth through discovery of numerous chemical modifications and development of conjugation chemistry to enable oligonucleotide delivery. Since his move to Alnylam in 2003, Dr. Manoharan worked to make siRNAs therapeutically viable using chemical modifications, siRNA conjugates, cationic lipids and other delivery systems. His research has embraced all major areas of oligonucleotide therapeutics, including antisense, RNAi, antagomirs, immunostimulatory oligonucleotides and pre-mRNA splicing modulation. Dr. Manoharan authored on over 180 publications and 160 issued US patents. In 2007 he was awarded American Chemical Society M. L. Wolfrom Award for contributions to Carbohydrate Chemistry.

Presentation Title

Chemical strategies for systemic delivery of RNAi drugs

Summary

Synthetic small interfering RNAs (siRNAs) act as therapeutic agents through RNA interference (RNAi) and are specific and potent inhibitors of gene expression. They can be designed to target diseases previously considered “undruggable”. Numerous studies, both in animal models and clinical trials, demonstrate broad potential therapeutic value of RNAi. Major challenge for successful development of RNAi therapeutics had been efficient delivery into organs/tissues and cells of interest, and its effective translation into clinic. Numerous delivery approaches have been developed over the years, and clinical trials are advancing with RNAi therapeutic candidates formulated in lipid nanoparticles (LNPs) for intravenous administration. We have also developed different conjugation strategies. Small molecule conjugation to siRNA may avoid side effects resulting from use of non-viral vectors, particles or excipient-based delivery systems. Chemical modifications, administration mode and nature of conjugated ligand play significant role in delivery. Our early work with cholesterol and other lipophile-conjugated siRNAs demonstrated enhanced siRNA bioavailability to multiple tissues including liver, either by systemic intravenous or local administrations. Uptake of siRNA-lipophile conjugates is facilitated by lipoprotein particles and associated receptors and by other ubiquitously expressed transmembrane proteins. Systemic and local applications of cholesterol-siRNA conjugates for various therapeutic targets have been well documented. Recently, systemic delivery of therapeutic siRNAs to liver hepatocytes by subcutaneous administration has been achieved using siRNAs conjugated to multiple N-acetylgalactosamine residues recognized by asialoglycoprotein receptor (ASGPR). ASGPR is expressed on cell surface of mammalian hepatocytes, recognizes exposed terminal galactose (Gal) and enables clearing of serum glycoproteins via clathrin mediated endocytosis. Recognition by ASGPR requires multi-valency with appropriate spatial orientation of Gal or analog N-acetylgalactosamine (GalNAc). siRNA-GalNAc conjugates efficiently target and silence disease-causing genes produced in liver hepatocytes. Using this conjugation platform, Alnylam is advancing several RNAi agents specific for liver targets through pre-clinical and clinical development to address genetically defined diseases with highly unmet medical need. Progress with siRNA-GalNAc conjugates and applications in several therapeutic areas will be presented.

William S. MARSHALL 博士

美国miRagen Therapeutics公司总裁兼首席执行官,董事会成员

William S. Marshall, Ph.D., is miRagen’s President, Chief Executive Officer, Co-Founder and Director. Prior to establishing miRagen, Dr. Marshall was Vice President of Technology and Business Development for Bioscience at Thermo Fisher Scientific. In this role, he was responsible for leading technology assessment and strategic planning for the Thermo Fisher Biosciences Division, a unit with revenues of approximately $1 billion that manufactures and supplies a wide range of products and services across the general-chemistry and life-sciences arenas.

Dr. Marshall was one of the scientific founders of Dharmacon, Inc., which was acquired by Fisher Scientific International, serving as the Executive Vice President for Research and Operations and General Manager. Prior to joining Dharmacon, Dr. Marshall served in many capacities at Amgen, Inc., most recently as Associate Director of Research, Site Head for Research and Head of the Nucleic Acid and Peptide Technology Department. In these positions, he participated in a variety of therapeutic development approaches throughout the drug discovery process leading to the development of clinical candidates.

Dr. Marshall earned his B.S. in Biochemistry from the University of Wisconsin-Madison and his Ph.D. in Chemistry in the laboratory of Professor Marvin Caruthers at the University of Colorado at Boulder. He is author and co-author of numerous research papers and patents. Dr. Marshall currently serves on the Boards of BiOptix, Inc., and the Colorado BioScience Association.

Presentation Title

Discovery and development of microRNA targeting therapeutics

Summary

Targeting microRNAs for inhibition or replacement allows for the manipulation of biological pathways that are important in a range of disease states.  As with any drug modality, it is vital to identify and validate the best target microRNA and drug pair that leads to the desired beneficial outcome in the disease state.  By applying a combination of genetic and pharmacological agent validation we have been able to identify compelling microRNA targets in several diseases with high unmet medical need.  We believe our strategy will allow us to advance multiple clinical candidates into innovative translational medicine studies allowing for rapid mechanistic proof of concept in humans.

Craig C. MELLO, PhD

University of Massachusetts Medical School, Howard Hughes Medical Institute, USA

2006 Nobel Prize Winner in Physiology or Medicine

Craig C. Mello is an Investigator of the Howard Hughes Medical Institute, holds the Blais University Chair in Molecular Medicine and is Co-director of the RNA Therapeutics Institute at the University of Massachusetts Medical School. His lab uses the nematode worm C. elegans as a model system to study embryogenesis and gene silencing. His collaborative work with Dr. Andrew Fire led to the discovery RNAi. Together they showed that exposing C. elegans to double-stranded ribonucleic acid (dsRNA) induces a sequence-specific silencing reaction that interferes with the expression of cognate cellular RNAs. RNAi, it turns out, is related to ancient gene-regulatory mechanisms found in both plants and animals. RNAi mechanisms are essential to life, and are now employed by scientists to explore the biological functions of genes, study disease processes and design new therapies. Dr. Mello earned a BSc from Brown and a PhD from Harvard, and he did postdoctoral work at the Fred Hutchinson in Seattle.  He then joined the University of Massachusetts Medical School as Assistant Professor, and has continued his research there ever since. Dr. Mello has received numerous prizes and awards for his research, including a Pew Scholarship, National Academy of Sciences, Rosenstiel, Gairdner Foundation, and Janssen Awards, the Wiley, MGH Warren Triennial, and Ehrlich-Darmstaedter Prizes, and, together with Andrew Fire, the 2006 Nobel Prize in Physiology or Medicine. Dr. Mello is a member of the National Academy of Sciences, the American Academy of Arts & Sciences, and the American Philosophical Society.

Presentation Title

RNA-guided genome defense and new frontiers in biotech and medicine

Summary

A breakthrough in the understanding of gene expression came with the realization that cells use RNA-guided search engines to identify and regulate both the DNA and other RNAs. First identified in a simple worm C. elegans as “RNA-interference” (RNAi), mechanisms related to RNAi have now been discovered in all domains of life. In RNAi-related mechanisms short pieces of genetic code in the form of RNA serve as search queries allowing the cell to rapidly identify and regulate genes in much the same way you type a short query into Google. Scientists can now enter synthetic RNA search queries into cellular search engines called Argonautes, and recently CAS9/CRISPR, allowing them to precisely cut any cellular RNA or DNA. The result is an unprecedented revolution in molecular genetics that promises to help unlock the secrets of life, and to speed the discovery of new medicines. This talk will describe how organisms use these remarkable mechanisms to program gene expression, and how scientists and physicians are learning to use them as tools. But, what this talk is really about is the excitement of science and the ever unfolding and deepening mysteries of life.

Brett P. MONIA 博士

美国Isis 制药公司高级副总裁

Oligonucleotide Therapeutics Society当选主席

Dr. Monia is a founding member of Isis Pharmaceuticals and Senior Vice President of Antisense Drug Discovery. Dr. Monia is also the Franchise Leader for Research and Development of Programs in Oncology and Rare Genetic Diseases at Isis Pharmaceuticals. As head of Drug Discovery, Dr. Monia is responsible for establishing strategic directions for preclinical drug discovery research focused on RNA-directed therapeutic platforms, establishment and supervision of early clinical development strategies through clinical proof-of-concept, and coordinating research activities with clinical investigators, consultants, and with corporate partners. His contributions include research into the medicinal chemistry and mechanisms of action of oligonucleotide-based drugs in cell culture and in animals, and in the establishment of numerous preclinical and clinical programs in various therapeutic areas, including oncology, metabolic disease, inflammation, cardiovascular disease, and rare diseases.

Programs under Dr. Monia’s direct supervision have resulted in the clinical development of more than thirty antisense-based drugs to date, covering areas as diverse as cancer, type 2 diabetes, cardiovascular disease, asthma, and rare genetic diseases.

Dr. Monia’s publication record exceeds 200 primary research manuscripts, reviews and book chapters, and is an inventor on more than 100 issued patents. In addition, Dr. Monia serves on the Executive Committee of the International Rare Diseases Research Consortium, on the editorial boards for a number of scientific journals, and serves on the Board of Directors and as incoming President of the Oligonucleotide Therapeutics Society. Dr. Monia also holds a position as a scientific advisory board member with OncoGeneX Technologies, Inc., and is an adjunct professor of biology at San Diego State University where he lectures at the graduate level on pharmacology.

Dr. Monia received his Ph.D. in Pharmacology at the University of Pennsylvania and B.S. degrees in Molecular Biology and Analytical Chemistry at Stockton State College, in Pomona, New Jersey.

Presentation Title

Transforming Drug Discovery for Human Therapeutics with Antisense Technology

Summary

The antisense oligonucleotide drug platform has now emerged as an important, mechanistically validated and therapeutically proven approach for drug discovery.  This achievement is the result of a twenty-five year, multi-billion dollar investment involving academic research, biotechnology and large pharmaceutical companies.   The first systemic, chronically administered antisense oligonucleotide drug has now been FDA approved.  Moreover, dozens of antisense-based drugs are under evaluation in the final stages of clinical testing for a broad range of diseases, and registration applications are imminent.  Thus, the antisense drug platform has now emerged as the third drug platform for human therapeutics, alongside small molecules and antibodies.  This presentation will highlight the key achievements leading to the success of the antisense platform, and a vision toward its future role in human therapeutics.

• RNA Therapeutics for Drug Discovery

• Antisense Oligonucleotide Medicinal Chemistry

• Late Stage Clinical Antisense Programs

• Future Directions for RNA-Targeted Therapeutics

Matthew PORTEUS 博士

斯坦福大学医学院教授

CRISPR Therapeutics公司创办人

Dr Matthew Porteus is an associate professor of pediatrics, Department of Pediatrics; Divisions of Hematology/Oncology and Human Gene Therapy, at Stanford School of Medicine. His research is focused on developing homologous recombination-based therapies for genetic and other diseases. He has a clinical practice at the Lucille Packard Children’s Hospital, where he is an attending physician for the Pediatric Bone Marrow Transplant Service.

Dr. Porteus graduated Magna Cum Laude from Harvard University before completing his MD and PhD degrees at Stanford. His PhD focused on the molecular biology of mammalian forebrain development. He completed his residency training in pediatrics at Boston Children’s Hospital, and his fellowship training in Pediatric Hematology/Oncology at Boston Children’s Hospital and the Dana Farber Cancer Institute. For his post-doctoral work, Dr. Porteus trained with Dr David Baltimore at the Massachusetts Institute of Technology (MIT) and the California Institute of Technology. It was during his post-doctoral work that he began studying genome editing, and he was the first to show that engineered nucleases could be used to precisely modify human cells by homologous recombination. Dr. Porteus was an assistant professor of pediatrics and biochemistry at UT Southwestern Medical School in Dallas before returning to Stanford in 2010 to take up his current role.

Presentation Title

Genome Editing using Engineered Nucleases

Summary

It is now possible to modify the genome with spatial and nucleotide precision using genome editing.  This has been made possible through the concerted efforts of a wide range of researchers with the integration of exciting discoveries from a diverse fields.  In this presentation I will discuss the range of different specific genome modifications that can be generated using both nuclease and non-nuclease mediated approaches. These precise modifications can be generated by harnessing the cell’s own endogenous DNA double-strand break repair pathways including non-homologous end-joining and homologous recombination.  Moreover, there are now a number of different engineered nuclease platforms that can be utilized for precisely modifying the genome including the use of modified homing endonucleases, zinc finger nucleases, TAL effector nucleases, RNA guided endonucleases of the CRISPR/Cas9 family, and mega-TAL nucleases. The advantages and disadvantages of each of these different nuclease platforms will be discussed. In sum, there is tremendous potential in using genome editing to develop novel therapeutics for human disease and the promise and challenges of fulfilling this potential will be discussed.

Georg SCZAKIEL 博士

德国吕贝克大学教授

Georg Sczakiel (Ph.D., Biology), is full Professor of Molecular Life Sciences, Director of the Institute of Molecular Medicine, Chairman of the Clinical Research Facility, and Chairman of the Committee for Good Scientific Practice of the University of Luebeck, Germany. He is executive Editor of Nucleic Acids Research and board member of various scientific journals. He got his Diploma in Chemistry at the University of Freiburg, his Doctor’s degree (Ph.D.) at the Max-Planck-Institute and University of Heidelberg, his Habilitation and Venia Legendi in Theoretical Medicine at the University of Heidelberg. Dr. Sczakiel spent his Post-Doc and the time as independent group leader at the German Cancer Research Center (DKFZ) under the mentorship of Prof. Dr. H. zur Hausen (Nobel Laureate). In Heidelberg he was also affiliated with the Steinbeis Transfer Center for Genome Informatics. He is one of the five founders of the Oligonucleotide Therapeutics Society (OTS). Currently Dr. Georg Sczakiels’ research focuses on the fundamental biochemical and cellular mechanisms of RNA-RNA recognition, on RNA interference, on the design and clinical application of oligonucleotide-based drugs, on new non-invasive RNA-based diagnostics of urological cancer including bladder cancer, and on the therapeutic application of nucleic acids in the field of chronic inflammation.

Presentation Title

Target RNA is involved in guide strand loading of Argonaute-2 and siRNA-induced RNA interference

Summary

Human Argonaute-2 (Ago2) is loaded by target-specific guide RNA from duplex siRNA resulting in the formation of biologically active RISC. Two independent lines of experimental evidence suggest the involvement of target RNA in Argonaute-2-loading by guide RNA. Firstly, competition of siRNA-induced RNAi by heterologous siRNA requires the competitor-specific target RNA for competition. Secondly, in an artificial sequence system with no homology to human sequences, Ago2 selectively associates with the strand of duplex siRNA which is complementary to target-RNA. Our observations are consistent with a model in which activation of RISC requires a first round of target suppression/cleavage.

宋尔卫博士

中山大学孙逸仙纪念医院副院长

长江学者特聘教授

Professor Song graduated from Zhongshan School of medicine, Sun Yat-sen University. He received his MD degree from Sun Yat-sen University in 2000. In 1999 and 2002, he joint the medical school of the University Duisburg-Essen in German and Harvard’s CBR Institute for Biomedical Research in US as a postdoctoral fellow, respectively. He was promoted as an instructor of Harvard medical school in 2004. In the same year, he went back to Sun Yat-sen university and appointed as a researcher in Sun Yat-sen University. In 2007, he was appointed as National Chang-Jiang scholar by the Ministry of education of P.R.China. In 2009, he was rewarded as Chinese medical board (CMB) distinguished professor and promoted as the chief scientist of the National key fundamental research project (973 project). He is the member of Standing Committee of the Chinese Anti-Cancer Association, committee of breast cancer society. He is the chairman-elect of the Guangdong Anti-Cancer association, committee of breast cancer society. Professor Song and his team is dedicated in basic research concerning the biology of breast cancer and its therapeutic strategies. His distinguished researches are sponsored by National Science Foundation for Distinguished Young Scholars of China, the State Key Program of National Natural Science of China, A3 foresight Program by National Natural Science Foundation of China, the Special Program for Key Basic Research of the Ministry of Science and Technology of China, the key Clinical Program of the Ministry of Health of China and the exploratory program of the 863 project. His works were honored as one of the top 10 breakthroughs of the year in 2003 by Science and one of the top 10 breakthroughs in Chinese University by Ministry of Education in China. He was the corresponding author or the first author in 48 articles that published in《Cell》、《Cancer Cell》、《Nature Medicine》、《Nature Biotechnology》、《Science Translational Medicine》、《Journal of Biological Chemistry》、《Oncogene》、《Clinical Cancer Research》、《Journal of Virology》、《Surgery》、《Kidney International》、《British Journal of Cancer》 and 《ACS Nano》, the total Impact factor is more than 346.3, these articles have been cited for more than 2900 times before July, 2014. As a co-author, he published 30 articles in journals such as 《PNAS》 and 《Blood》. He was the Chief editor of the 《The biological rational and application of RNA interference.》, which was published by the Higher education press. He was also the Chief editor of the 《Small RNA: Basic Research and Clinical Application》, which was published by the Beijing Technology press. He was also one of the authors of 《Gene Silencing by RNA Interference: Technology and Application》 that published by CRC Press.

Key Recent Publications:

1. Su S*, Liu Q*, Chen J, Chen J, Chen F, He C, Huang D, Wu W, Lin L, Huang W, Zhang J, Cui X, Zheng F, Li H, Yao H, Su F, Song E#. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell 2014.

2. Chen J*, Yao Y*, Gong C*, Yu F*, Sun S, Chen J, Liu B, Deng H, Wang F, Lin L, Yao H, Sun F, Karen S. Anderson, Liu Q, Mark E. Ewen, Yao X#, Song E#. CCL18 from Tumor-Associated Macrophages Promotes Breast Cancer Metastasis via PITPNM3. Cancer Cell 2011; 19(4), 541–555.

3. Yao Y*, Sun T*, Huang S, Dou S, Lin L, Chen J, Ruan J, Mao C, Yu F, Zeng M, Zhang J, Liu Q,  Su F, Zhang P, Lieberman J#, Wang J#, Song E#. Targeted Delivery of PLK1-siRNA by ScFv Suppresses Her2+ Breast Cancer Growth and Metastasis. Science Translational Medicine 2012; 4:130ra48.

Presentation Title

BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10

Summary

Long noncoding RNAs (lncRNAs) are a large class of RNA molecules involved in a variety of biological processes. Presently, only a small number of lncRNAs have been characterized to control gene expression as decoys, guides or scaffolds mainly in the nuclei to interact with DNA, RNA or gene-regulatory proteins. However, the roles of many lncRNAs located in the cytoplasm are unknown. Here, we demonstrate that the expression of a cytoplasmic NF KappaB Interacting LncRNA (NKILA) is upregulated in breast cancer cells by inflammatory stimuli through NFkB signaling. However, silencing NKILA in the presence of inflammatory stimuli further promotes inflammation-induced NFkB activation, leading to enhanced EMT and reduced apoptosis in tumor cells and increased cancer metastasis in vivo. Additionally, ectopic NKILA expression inhibits NFkB activation and the ensuing cancer invasion and metastasis, suggesting that NKILA is a negative regulator of NFkB signaling. Indeed, NKILA prevents activation of NFkB by interacting with the NFkB complex in the cytoplasm and inhibits IKK-induced phosphorylation and degradation of IkB. We further identify that the 5’-region of NKILA harbors a mimicry of NFkB binding motif that interacts directly with NFkB p65. Moreover, the3’-region of the p65-engaged NKILA directly masks the phosphorylation motif of IkB to block its phosphorylation by IKK. These findings indicate a new mechanism by which cytoplasmic lncRNAs directly regulate the activation of major signaling molecules and participate in the auto-regulatory feedback circuitry of signaling pathways in cancer cells, thus uncovering a previously unappreciated crosstalk between lncRNAs and signaling molecules that underlies cancer-related inflammation.

René Thürmer, PhD

Deputy Head of the Unit Pharmaceutical Biotechnology, BfArM – Federal Institute for Drugs and Medical Devices, Germany

Dr. René Thürmer received his diploma in chemistry and his Ph.D. in biochemistry from the University of Tübingen. He joined the BfArM (Federal Institute for Drugs and Medical Devices, Bonn, Germany) in 2000. He currently serves as a CMC reviewer and is Deputy Head of the Unit Pharmaceutical Biotechnology.

His experience is in the field of formulation, manufacture and control of medicinal products, in particular in the field of peptides, proteins, liposomes, sustained release polymer drug products, depot formulations, polymer-conjugated drug products, natural and synthetic surfactants, nanomedicine and others. His special focus lies on oligonucleotide preparations.

Presentation Title

Regulatory Aspects of Nucleic Acids Therapeutics

Summary

Working in the field of synthetic oligonucleotides is extremely fascinating. Synthetic oligonucleotides are an exciting class of therapeutic products that are under development for a variety of indications. Many of them have been developed to address significant medical needs that are so far unmet.

Characterization and quality control testing are required throughout the clinical development of oligonucleotides intended for therapeutic use. Detailed information on structural characterization studies that supports the designation of these properties or characteristics should be provided in submissions to regulatory agencies worldwide.

What to control is one of the key questions in connection with regulatory submissions during clinical development and marketing authorization applications.

This presentation will provide an overview about the regulatory landscape for oligonucleotides. Issues related to the pharmaceutical quality of oligonucleotides are highlighted. Since the early and open communication with Regulatory Agencies can significantly reduce time to market for a new drug product ways of interaction are exposed.

Micky D. TORTORELLA 博士

中国科学院广州生物医药与健康研究院新药研发与技术转化首席技术官

Micky Tortorella is former Senior Principal Investigator at Pfizer (2001-2009) with 15 years of experience in the pharmaceutical industry. Prior to working at Pfizer he had a successful tenure as a Research Scientist at DuPont Pharmaceuticals (1993-1999). Previous work focused on understanding the biochemical mechanisms involved in the turnover and degradation of the cartilage matrix, which led to the discovery of ADAMTS-4 and -5, enzymes responsible for matrix catabolism in arthritic diseases and cancer. Micky Tortorella has led and provided direction to multiple discovery teams applying basic biology to the drug discovery process, including identification of novel targets, innovation in assay development and the advancement of small molecule inhibitors into clinical trials. He is regarded as a key opinion leader in the United States as well as internationally in osteoarthritis, metalloproteinase biology and in drug discovery with over 50 publications in top tier journals and 12 US and international patents.

Micky Tortorella recently joined GIBH in May 2009 and is responsible for creating and leading an integrated drug discovery centre focused on developing disease modifying pharmaceutical drugs in the areas of oncology, CNS, infectious diseases and arthritis.

Responsibilities:

1. Establish the overall strategic direction for the DDP.

2. Provide leadership to enable the discovery of new targets and the development of innovative therapeutics in response to unmet medical needs in multiple therapeutic areas.

3. Insure that a sufficient number of new chemical entities are successfully promoted to the development track each year.

4. Coordinate the successful creation of new companies in China.

Chen-Yu ZHANG (张辰宇) 博士

南京大学生命科学学院教授,院长

Chen-Yu Zhang earned his PhD in Molecular Endocrinology from Tokushima University, Japan in 1995. He has studied Mitochondria function and Metabolism at MIDMC and Harvard Medical School as a postdoctoral fellow (1995-2000) and a Research Assistant Professor (2000-2004). Dr Zhang has been the Dean and Professor of School of Life Sciences, Nanjing University, China since 2003. Dr Zhang has found firstly that the circulating microRNA serves as a novel class of non-invasive biomarker for diseases and can be used to diagnosis, prognosis, etc. He has reported that the secreted microRNA is the novel class of signaling molecule in mediating inter-cellular/inter-organ communication. Most recently, Dr Zhang has reported that functional exogenous plant microRNAs could be absorbed by human and animal. The absorbed exogenous plant microRNA regulated mammalian gene and human and animal’s physiology/pathophysiology in a cross-kingdom manner. Dr Zhang is one of the pioneers discovered extracellular RNA (exRNA) field。 He published more than 120 peer-reviewed publications from the project and applied over 40 international patents related to exRNA.

Presentation Title

Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses

Summary

A plant microRNA, MIR2911, which is enriched in honeysuckle, directly targets influenza A viruses (IAV) including H1N1, H5N1 and H7N9. Drinking of honeysuckle soup can prevent IAV infection and reduce H5N1-induced mice death. It is the first demonstration that a natural product can directly target virus. Furthermore, one of their ongoing studies shows that MIR2911 also directly targets Ebola virus. Thus, MIR2911 is able to serve as the “viral penicillin” to directly target various viruses. These results also provide another evidence to prove their previous discovery that dietary exogenous miRNAs are able to be functionally absorbed by mammalian gastrointestinal tract and play an important regulatory role in a cross-kingdom manner.

       论坛起源于广州核酸国际论坛,在政府及各界支持下已经连续举办了五届,历届大会报告人汇集诺贝尔奖得主在内的全球顶级科学家、学者和企业家,论坛聚焦精准医学、生命科学、基因治疗、核酸药开发等最新热点进展,分享来自全球范围内核酸研究及应用的重大成果和进展。中国核酸国际论坛(CNAF)的知名度与影响力也受到国际学术界与企业界的高度赞誉,被誉为中国核酸研究与产业化的重要风向标。