第三届广州核酸国际论坛

2015年11月18-19日 , 广州科学城

议题介绍
随着近年来非编码RNA、基因组学和CRISPR基因编辑等核酸领域突飞猛进地发展,本届论坛将邀请20多位世界顶尖科学家及知名企业家齐聚一堂,与您分享本领域的最新成果和进展。本届CNAF会议主题如下:

1、前沿核酸科学

2、尖端核酸技术

3、基于核酸的诊断与分子标志物

4、核酸技术治疗和其他应用

论坛议程

Day 1 Wednesday, November 18

08:45-08:55 Opening Organizers
08:55-09:00 Chair Takanori Yokota, MD, PhD
09:00-09:45 Keynote Eric D. Green, MD, PhD, Director, National Human Genome Research Institute (NHGRI), NIH, USA
Title: Human genomics, precision medicine, and advancing human health
09:45-10:15   Oleg Iartchouk, PhD, Global Head of Genomics, Novartis, USA
Title:
 NGS in drug discovery research
10:15-10:45 Tea Break
10:45-11:15   Todd Lowe, PhD, Professor, University of California Santa Cruz, USA
Title:
 Unraveling the complex roles for 500+ human tRNA genes and the ubiquitous, overlooked
tRNA fragments
11:15-11:45   Mark A. Kay, MD, PhD, Professor, Stanford University School of Medicine, USA
Title:
 New adeno associated vector (AAV) approaches for episomal and site-specific integration
based gene/RNAi therapeutics
11:45-12:00 Technology Huanming Yang, PhD, Professor and Chairman, BGI, China
Title: 
From the HGP to “Precision Medicine”
12:00-13:30 Lunch
13:30-13:35 Chair Laura Sepp-Lorenzino, PhD
13:35-14:20 Keynote Jack W. Szostak, PhD, Professor, Harvard Medical School, 2009 Nobel Prize Winner, USA
Title:
 The origins of cellular life
14:20-14:50   Takanori Yokota, MD, PhD, Professor, Tokyo Medical and Dental University, Japan
Title:
 DNA/RNA heteroduplex oligonucleotide – a novel concept of therapeutic oligonucleotides
14:50-15:20 Tea Break
15:20-15:50   Seyed M. Moghimi, PhD, Professor, University of Copenhagen, Denmark
Title:
 Integrative nanomedicine: phage-derived peptidic assemblies for therapeutic nucleic acid
delivery targeting two receptors
15:50-16:20   Daniel G. Anderson, PhD, Professor, Massachusetts Institute of Technology, USA
Title:
 Nucleic acid delivery systems for RNA therapy and gene editing
16:20-16:50   A. Robert Macleod, PhD, Vice President, Isis Pharmaceuticals, USA
Title:
 Next generation constrained ethyl (cEt) antisense oligonucleotide inhibitors for therapeutic
targeting of extra hepatic tissues including tumors
16:50-17:00 Day End Organizers

Day 2 Thursday, November 19

08:50 – 09:00 Chair Nikolaus Rajewsky, PhD
09:00-09:45 Keynote Craig C. Mello, PhD, Professor, University of Massachusetts, 2006 Nobel Prize Winner, USA
Title:
 RNA guided genome surveillance
09:45-10:15   Michael P. Terns, PhD, Professor, University of Georgia, USA
Title:
 CRISPR-Cas: small RNA mediated prokaryotic immune systems
10:15-10:45 Tea Break
10:45-11:15   Udi Qimron, PhD, Professor, Tel Aviv University, Israel
Title:
 CRISPR/Cas-encoding bacteriophages programmed to sensitize and kill antibiotic-resistant
bacteria
11:15-11:45   Joanne Kamens, PhD, Executive Director, Addgene, USA
Title:
 Trends in CRISPR technologies: data from Addgene’s plasmid repository
11:45-12:00 Technology Xingwang Fang, PhD, Thermo Fisher Scientific, USA
Title:
 Sample prep for next generation molecular testing

Xiquan Liang, PhD, Thermo Fisher Scientific, USA
Title:
 Rapid and highly efficient mammalian cell engineering via Cas9 protein transfection

12:00-13:30 Lunch
13:30-13:35 Chair Mark A. Kay , MD, PhD
13:35-14:20 Keynote Thomas A. Steitz, PhD, Professor, Yale University, 2009 Nobel Prize Winner, USA
Title:
From the structure and function of the ribosome to new antibiotics
14:20-14:50   Nikolaus Rajewsky, PhD, Professor, Max Delbrück Center for Molecular Medicine, Germany
Title:
 Regulatory RNAs
14:50-15:20 Tea Break
15:20-15:50   Zhou Songyang, PhD, Professor, Sun Yat-sen University, China; Baylor College of Medicine, USA
Title:
 Gene editing in mouse and human cells
15:50-16:20   Dong-ki Lee, PhD, Professor, Sungkyunkwan University, South Korea
Title:
 Therapeutic development using the second generation RNAi triggers
16:20-16:50   Laura Sepp-Lorenzino, PhD, Vice President, Alnylam Pharmaceuticals, USA
Title:
 Hepatocyte targeted RNAi therapeutics: case studies in rare diseases and hepatitis B
16:50-17:00 Closing Craig C. Mello, PhD, Professor, University of Massachusetts, 2006 Nobel Prize Winner, USA
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演讲嘉宾

Daniel G. ANDERSON, PhD

Professor, Massachusetts Institute of Technology, USA

Dr. Daniel G. Anderson is an Associate Professor at the Massachusetts Institute of Technology, and a member of the Department of Chemical Engineering, the Institute of Medical Engineering and Science, and the David H. Koch Institute for Integrative Cancer. He received his PhD in molecular genetics from the University of California at Davis. At MIT, he pioneered the use of robotic methods for the development of smart biomaterials for drug delivery and medical devices. His work has led to the first methods rapid synthesis, formulation, analysis, and biological evaluation of large libraries of biomaterials for use in medical devices, cell therapy and drug delivery. In particular, the advanced drug delivery systems he has developed provide new methods for nanoparticulate drug delivery, non-viral gene therapy, siRNA delivery, and vaccines. His work has resulted in the publication of over 230 papers, patents and patent applications. These patents have led to a number of licenses to pharmaceutical, chemical and biotechnology companies, and a number of products that have been commercialized or are in clinical development.

Presentation Title
Nucleic acid delivery systems for RNA therapy and gene editing

Summary

High throughput, combinatorial approaches have revolutionized small molecule drug discovery. Here we describe our work on high throughput methods for developing and characterizing RNA delivery and gene editing systems. Libraries of degradable polymers and lipid-like materials have been synthesized, formulated and screened for their ability to delivery RNA, both in vitro and in vivo. A number of delivery formulations have been developed with in vivo efficacy, and show potential therapeutic application for the treatment of genetic disease, viral infection, and cancer.

Eric D. GREEN, MD, PhD

Director, National Human Genome Research Institute (NHGRI), NIH, USA

For over a quarter century, Dr. Green has been at the forefront of efforts to map, sequence, and understand eukaryotic genomes. His work included significant, start-to-finish involvement in the Human Genome Project; these initial efforts latter blossomed into a highly productive program in comparative genomics that provided important insights about genome structure, function, and evolution. Now, as Director of NHGRI, Dr. Green is responsible for providing overall leadership of the Institute’s research portfolio and other initiatives. In 2011, Dr. Green led NHGRI to the completion of a strategic planning effort that yielded a new vision for the future of genomics research, entitled “Charting a course for genomic medicine from base pairs to bedside” (Nature, 470:204-213, 2011).

Dr. Green received his BS in bacteriology from the University of Wisconsin at Madison in 1981 and both a PhD in cell biology and an MD in 1987 from Washington University in St. Louis. For his PhD, Dr. Green studied sugar molecules that are attached to proteins. From 1987 to 1992, he was a resident in laboratory medicine at the Washington University School of Medicine, serving as Co-Chief Resident from 1990 to 1992. Discussions about a possible Human Genome Project in the late 1980s coupled with his clinical interests in molecular diagnostics prompted him to join the laboratory of Maynard V. Olson, Ph.D. as a postdoctoral research fellow to work in the then-emerging field of genomics. In 1992, Dr. Green was appointed Assistant Professor of Pathology, Genetics, and Internal Medicine at the Washington University School of Medicine, as well as Co-Investigator in the University’s Human Genome Center. In 1994, Dr. Green was recruited to join the newly formed Intramural Research Program of the then-named National Center for Human Genome Research (NCHGR) at the National Institutes of Health. Two years later, he earned tenure; that same year, he was also appointed Chief of the Genome Technology Branch. In 1997, he became the Founding Director of the NIH Intramural Sequencing Center (NISC). Dr. Green then became the third Director of the National Human Genome Research Institute (NHGRI) in December 2009.

Honors given to Dr. Green include a Helen Hay Whitney Postdoctoral Research Fellowship (1989-1990), a Lucille P. Markey Scholar Award in Biomedical Science (1990-1994), induction into the American Society for Clinical Investigation (2002), an Alumni Achievement Award from Washington University School of Medicine (2005), induction into the Association of American Physicians (2007), a Distinguished Alumni Award from Washington University (2010), the Cotlove Award from the Academy of Clinical Laboratory Physicians and Scientists (2011), and the Wallace H. Coulter Lectureship Award from the American Association for Clinical Chemistry (2012). He is a Founding Editor of the journal Genome Research (1995-present) and a Series Editor of Genome Analysis: A Laboratory Manual (1994-1998), both published by Cold Spring Harbor Laboratory Press. He is also Co-Editor of Annual Review of Genomics and Human Genetics (since 2005). Dr. Green has authored and co-authored over 300 scientific publications.

Presentation Title
Human genomics, precision medicine, and advancing human health

Summary
Starting with the launch of the Human Genome Project in 1990, the past quarter-century has brought spectacular achievements in genomics that dramatically empower the study of human biology and disease. The human genomics enterprise is now in the midst of an important transition, as the growing foundation of genomic knowledge is being used by researchers and clinicians to tackle increasingly complex problems in biomedicine. Of particular prominence is the use of revolutionary new DNA sequencing technologies for generating prodigious amounts of DNA sequence data to elucidate the complexities of genome structure, function, and evolution, as well as to unravel the genomic bases of rare and common diseases. Together, these developments are ushering in the era of genomic medicine.

 

Augmenting the advances in human genomics have been innovations in technologies for measuring environmental and lifestyle information, electronic health records, and data science; together, these provide opportunities of unprecedented scale and scope for investigating the underpinnings of health and disease. To capitalize on these opportunities, U.S. President Barack Obama recently announced a major new research endeavor— the U.S. Precision Medicine Initiative. This bold effort will be framed around several key aims, which include accelerating the use of genomically informed approaches to cancer care, making important policy and regulatory changes, and establishing a large research cohort of >1 million volunteers to facilitate precision medicine research. The latter will include making the partnership with all participants a centerpiece feature in the cohort’s design and development. The Precision Medicine Initiative represents a broad-based research program that will allow new approaches for individualized medical care to be rigorously tested, so as to establish a new evidence base for advancing clinical practice and, eventually, human health.

Oleg IARTCHOUK, PhD

Global Head of Genomics, Novartis, USA

Oleg Iartchouk received his Ph.D. in molecular biology from Moscow State University. For last 15 years he was in charge of genomics laboratories within several biotechnology and pharmaceutical companies. His laboratory was an early adopter of the NGS technologies and applied it to different genomics problems within drug discovery research. Within his current role as the genomics head at Novartis Oleg applies NGS to multiple Disease areas and functional platforms. Dr. Iartchouk co-authored numerous research articles, patent applications. He also presented at multiple scientific conferences around the world.

Presentation Title

NGS in drug discovery research

Summary

Next generation sequencing is the breakthrough technology that promotes big data driven approaches in drug discovery research. Several examples of successful NGS applications that create new paradigm will be presented and explained. Future trends for next generation sequencing will be outlined.

Joanne KAMENS, PhD

Executive Director, Addgene, USA

Dr. Kamens is the Executive Director of Addgene, a mission driven, nonprofit dedicated to helping scientists around the world share plasmid reagents. She received her PhD in Genetics from Harvard Medical School then spent 15 years at BASF/Abbott. In 2007 she joined RXi Pharmaceuticals as Senior Director of Research. Dr. Kamens founded the current Boston chapter of the Association for Women in Science and in 2010, Dr. Kamens received the Catalyst Award from the Science Club for Girls for longstanding dedication to empowering women in STEM. In 2013, she was named one of PharmaVoice’s 100 Most Inspiring Commanders & Chiefs. Dr. Kamens serves on a number of nonprofit boards and speaks widely on plasmid sharing, science careers and diversity in person and via webinar. She currently blogs at blog.addgene.org and can be reached via https://www.linkedin.com/in/joannekamens

Presentation Title
Trends in CRISPR technologies: data from Addgene’s plasmid repository

Summary
Addgene (www.addgene.org) is a nonprofit organization that accelerates biomedical research and discovery by improving access to useful research materials and data. To fulfill this mission, Addgene has worked with >2,400 laboratories to collect high-quality published plasmids that can then be distributed to scientists in >600 academic institutions in 83 countries. The repository is always expanding to provide access to the most current materials. Repositories play a key role in helping scientists share internationally, improving reproducibility, and optimizing use of limited resources.

 

Addgene has played a unique role in the rapidly expanding field of CRISPR/Cas9-mediated genome engineering. In January 2013, the first papers describing the use of CRISPR/Cas9 for genome engineering were published and many of the early leaders in this field were already strong supporters of Addgene’s mission. Addgene’s “open source” distribution model has facilitated rapid advances in the field. A search of google.scholar with the words “CRISPR AND Addgene” retrieves >1,400 publications, demonstrating the impact of efficient materials dissemination to support rapid paths to novel findings and publications. Data on distribution of plasmids for various genome engineering technologies will be presented along with an overview of the many available reagents in the Addgene Collection.

Mark A. KAY, MD, PhD

Professor, Stanford University School of Medicine, USA

Dr. Kay is the Head of the Division of Human Gene Therapy and serves as the Associate Chair of Research in Pediatrics. He received a Ph.D. in Developmental Genetics, and M.D. from Case Western Reserve in Cleveland, Ohio. Before coming to Stanford in 1998, Dr. Kay was at the University of Washington as Associate Professor in the Departments of Medicine, Biochemistry and Pathology. Dr. Kay has received many awards. Dr. Kay was on the founding board of directors of the American Society for Gene Therapy and served as the Society’s Vice-President, President-Elect, and President in 2003-2006. He is on Board of Directors of the Oligonucleotide Therapeutics Board of Directors. He was elected to the Association of American Physicians in 2010. Dr. Kay received the American Society for Gene and Cell Therapy’s Outstanding Investigator Award in 2013. He is a scientific founder of Voyager Therapeutics and LogicBio Therapeutics.

Dr. Kay has published over 250 scientific papers. The focus of the laboratory is to establish the scientific principles required for gene and nucleic acid transfer for the treatment of genetic and acquired diseases. Dr. Kay has worked on the development of many DNA gene transfer vectors and the mechanism by which they transduce tissues in mammals. His group has performed two Phase I/II gene therapy trials for hemophilia B. His laboratory was the first to establish therapeutic RNAi in whole non-embryonic mammals, and RNAi-mediated inhibition of a human viral pathogen (HBV) in animals. His work continues towards defining the molecular limits of delivered and expressed RNAi in vivo as well as the mechanisms involved in si/shRNA -mediated gene silencing and the biological mechanisms involved in miRNA-mediated gene repression. In addition, his laboratory is studying the role that a newly discovered small non-coding RNA plays in mammalian gene regulation.

Presentation Title
New adeno associated vector (AAV) approaches for episomal and site-specific integration based gene/RNAi therapeutics

Summary
•Mice with chimeric human-murine livers may be a better predictor (compared to any other animal model) of rAAV vector efficacy in humans
•This animal model can be used in combination with multi-species AAV capsid libraries to select for rAAV vectors with novel transduction properties
•A new rAAV vector capable of site-specific integration overcomes some of the limitations of canonical rAAV-based gene transfer and has been used to treat animal models of human disease
•These new vector strategies can be used to express therapeutic proteins or short-hairpin non-coding RNAs (e.g. Transcriptional RNAi)

Dong-ki LEE, PhD

Professor, Sungkyunkwan University, South Korea

Chief Executive Officer, OliX Pharmaceuticals

Prof. Dong-ki Lee received B. S. in Chemistry from Korea Advanced Institute of Science and Technology (KAIST) in 1993, and Ph. D. in Biochemistry from Cornell University in 1999. After post-doctoral training in Pohang University of Science and Technology (POSTECH), Toolgen Inc., and KAIST, he joined POSTECH as an assistant professor in 2004. In 2008, He moved to Sungkyunkwan University and is a full professor of Chemistry since 2012. In 2008, Prof. Lee was selected as the principal investigator of the Global Research Laboratory program, funded by Korean government, to develop novel RNAi medicine. He is currently serving as the Asian editor of “Nucleic Acid Therapeutics” and a editorial board member of “Molecular Therapy: Nucleic Acids”. His work on novel siRNA structures, nucleic acid aptamers, and eukaryotic gene regulation has been published as over 70 papers including prestigious journals such as Nature, Cell, PNAS, and Molecular Therapy. In 2010, he founded OliX Pharmaceuticals, a RNAi therapeutics company focusing on topically administrable diseases, and serves as Chief Executive Officer.

Presentation Title
Therapeutic development using the second generation RNAi triggers

Summary
Recent studies came up with novel RNAi triggering molecular structures with unique structural features and functional advantages compared with the conventional siRNA. In this seminar, I will introduce novel RNAi triggers developed in my laboratory, with improved features over conventional siRNA, such as reduced off-target effects, enhanced cellular delivery when complexed with cationic delivery vehicles, and specific target gene silencing combined with immunostimulation. One of these second generation RNAi triggers, asymmetric siRNAs (asiRNAs), were combined with specific set of chemical modifications to generate cell-penetrating asiRNAs (cp-asiRNAs), which can execute gene silencing without delivery vehicle both in vitro and in vivo. I will introduce current therapeutic development programs based on the cp-asiRNA structures.

Todd LOWE, PhD

Professor, University of California Santa Cruz, USA

Co-founder and Chief Scientist, Maverix Biomics

Todd Lowe earned his Ph.D. in molecular genetics from Washington University in St. Louis in 1999, and helped identify the non-coding RNA genes in many of the first eukaryotic and archaeal genomes sequenced using his search tools. He then studied as a post-doctoral scholar at Stanford University with David Botstein in the Functional Genomics microarray group. Dr. Lowe was recruited to the University of California, Santa Cruz in 2001 to co-found the Department of Biomolecular Engineering, where he integrates molecular and computational biology to investigate non-coding RNAs and RNA-based gene regulation. With software developed in his lab and analyses distributed by the Genomic tRNA Database, Dr. Lowe has become a world expert in tRNA biology. Most recently, Dr. Lowe’s lab has been studying the functional impacts of dynamic RNA modification in the cell, including the dense, poorly understood modifications in transfer RNAs, and the ubiquitous tRNA fragments found in the cell and extracellular microvesicles. Dr. Lowe’s lab develops new RNA-seq library construction methods paired to custom computational analytics to enable exploration of these new frontiers of RNA biology.

Presentation Title

Unraveling the complex roles for 500+ human tRNA genes and the ubiquitous, overlooked tRNA fragments

Summary

High throughput RNA sequencing has accelerated discovery of the regulatory roles of many small RNAs, but RNAs containing “hard stop” modifications have largely escaped detection due to interference with reverse transcription during RNA-seq library preparation. I will describe new methods that enable transcriptome-scale mapping of highly modified RNAs, as well as an efficient method to identify and monitor changes in the abundance or modification state of any small RNA with these modifications. Using these methods, we are finally able to begin unraveling the complex regulatory programs of hundreds of unique human tRNAs, as well as to explore the large number of mostly overlooked tRNA-derived RNAs, some of which have already been linked to control of global translation rates, cancer cell proliferation, apoptosis, and core metabolic pathways.

A. Robert MACLEOD, PhD

Vice President, Ionis Pharmaceuticals, USA

Dr. MacLeod is currently the Vice President of Oncology Drug Discovery at Ionis Pharmaceuticals, a biotechnology company focused on RNA targeted therapeutics. Dr. MacLeod obtained his undergraduate degree in Chemistry and Biochemistry from Concordia University in Montreal, Canada and his doctoral degree from McGill University, Montreal in 1995. As part of his Ph.D studies, Dr. MacLeod demonstrated for the first time that Epigenetic regulators of gene expression (the DNA Methyltransferase enzymes) played active roles in cancer and that these were in fact attractive cancer drug targets. His Doctoral work led to the creation of MethylGene Inc. a biotechnology company focused on small molecule inhibitors of Epigenetic targets. Dr. Macleod later became the first scientist and Director of Biology at MethylGene, and contributed to the discovery and clinical evaluation of several experimental oncology therapeutics including, Mocetinostat, MGCD265, MGCD516 and MG98. Dr. MacLeod gained his initial experience in antisense technology as a Post-Doctoral fellow at Ionis Pharmaceuticals under the supervision of Dr. Stanley T. Crooke (Chairman and CEO of Ionis). In this capacity he contributed to the identification of novel, non-RNase H terminating mechanisms for antisense drugs. Since returning to Ionis in 2008, Dr. MacLeod has been actively involved in the discovery and preclinical development of antisense drug candidates in the several therapeutic areas including, oncology, thrombosis, inflammatory and muscle diseases. These include the clinical stage compounds, FXIRX (now partnered with Bayer) for the treatment of thrombosis, DMPKRX for myotonic dystrophy (now partnered with Biogen) and PKKRX for angioedema. Under his direction the oncology team identified and advanced into clinical development the first two Generation 2.5 cEt ASOs STAT3RX(now AZD9150) and ARRX (now AZD5312), where robust single agent antitumor responses were demonstrated with STAT3RX in several tumor types, ultimately leading to the creation of a broad strategic collaboration between Ionis and AstraZeneca focused on the discovery and development of antisense drugs for the treatment of cancer.

Presentation Title

Next generation constrained ethyl (cEt) antisense oligonucleotide inhibitors for therapeutic targeting of extra hepatic tissues including tumors

Summary
Second generation MOE Gapmer antisense oligonucleotides have demonstrated great promise and clinical activity when employed as a therapeutic modality to target genes expressed in liver. However, the robust targeting of certain extra hepatic tissues, particularly tumors has been more challenging. This presentation will highlight recent advances with next generation cEt ASOs, including the preclinical proof of concept for targeting several extrahepatic tissues including tumors and the clinical translation of these findings to human cancer studies.

Craig C. MELLO, PhD

Professor, University of Massachusetts, USA

Howard Hughes Medical Institute

National Academy of Sciences

2006 Nobel Prize in Physiology or Medicine

Dr. Mello’s lab uses the nematode C. elegans as a model system to study embryogenesis and gene silencing. His collaborative work with Dr. Andrew Fire led to the discovery of RNA interference (RNAi), for which they shared the 2006 Nobel Prize in Physiology or Medicine. Together they showed that when C. elegans is exposed to double-stranded ribonucleic acid (dsRNA), a molecule that mimics a signature of viral infection, the worm mounts a sequence-specific silencing reaction that interferes with the expression of cognate cellular RNAs. Using readily produced short synthetic dsRNAs, researchers can now silence any gene in organisms as diverse as rice and humans. RNAi allows researchers to rapidly “knock out” the expression of specific genes and, thus, to define the biological functions of those genes. RNAi also provides a potential therapeutic avenue to silence genes that cause or contribute to diseases.

Dr. Mello received his BS degree in Biochemistry from Brown University in 1982, and PhD from Harvard University in 1990. From 1990 to 1994, he conducted postdoctoral research at the Fred Hutchinson Cancer Research Center in Seattle, WA. Now Dr. Mello is an Investigator of the Howard Hughes Medical Institute, the Blais University Chair in Molecular Medicine and Co-director of the RNA Therapeutics Institute at the University of Massachusetts Medical School.

Besides the Nobel Prize, Dr. Mello’s work was recognized with numerous awards and honors, including the National Academy of Sciences Molecular Biology Award (2003), the Wiley Prize in Biomedical Sciences from Rockefeller University (2003), Brandeis University’s Lewis S. Rosnstiel Award for Distinguished Work in Medical Research (2005), the Gairdner Foundation International Award (2005), the Massry Prize (2005), the Paul Ehrlich and Ludwig Darmstaedter Award (2006), the Dr. Paul Janssen Award for Biomedical Research (2006), the Hope Funds Award of Excellence in Basic Research (2008). He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the American Philosophical Society.

Presentation Title

RNA guided genome surveillance

Summary
Organisms experience a constant onslaught of invasive nucleic acids, such as viruses and transposable elements that cause genome instability and a broad range of diseases including cancer. The resulting arms race has driven the evolution of sophisticated nucleic acid-based immune pathways, such as RNA interference (RNAi) and prokaryotic CRISPR/CAS systems. The ability to recognize and respond to pathogenic nucleic acids, however, requires an equally sophisticated mechanism to avoid recognition and silencing of self-genes, or autoimmune silencing. Remarkably, this self/non-self dichotomy is regulated in C. elegans by opposing Argonaute pathways: the conserved Piwi pathway, which scans for and silences foreign genes, and the CSR-1 pathway, which recognizes and protects self-genes from Piwi-mediated autoimmune silencing. Both Argonautes and their small RNAs provide heritable epigenetic signals that confer stable modes of trans-generational gene regulation. We are exploring how CSR-1 interfaces with the conserved Piwi pathway, and the worm-specific AGO (WAGO) pathway to achieve whole-transcriptome surveillance of germline gene expression. We continue this journey into the surprising world of small RNAs with the hope that our research will shed new light on the mechanisms of transgenerational epigenetics inheritance and regulation of gene expression.

 

Seyed M. MOGHIMI, PhD

Professor, University of Copenhagen, Denmark

Seyed Moghimi earned his PhD in biochemistry in 1989 from Charing Cross Hospital Medical School, Imperial College (University of London). Afterwards, he completed a four-year post-doctoral training programme in Advanced Drug Delivery Research at the School of Pharmaceutical Sciences (University of Nottingham, UK) under the guidance of Prof. S.S. Davis. This was followed by a university fellowship position at Nottingham before joining the School of Pharmacy at the University of Brighton as a Senior Lecturer. In 2009 Moein joined University of Copenhagen as Professor of Nanomedicine and became the Director of the Centre for Pharmaceutical Nanotechnology and Nanotoxiocology. He is also an affiliated full member at the Department of Translational Imaging, Houston Methodist Research Institute, Houston Methodist Hospital Systems (Houston, Texas), adjoint professor at the Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Denver Medical Center, and visiting professor at Università Degli Studi Di Padova (Italy). Furthermore, Dr. Moghimi is cofounder of S & M Discovery Group (London, UK); a nanomedicine R&D and consulting venture. He has also been practicing in the capacity of consultant to over 50 pharmaceutical, biotechnology, health and food industries as well as investment banks, management consultancy firms and other entrepreneurial enterprises worldwide. He further acts as associate editor for Nanomedicine: NBM and Journal of Biomedical Nanotechnology and features on editorial board of another 15 international journals in drug delivery and nanomedicine. His research activities are focused on pharmaceutical nanoscience, and fundamental nanomedicine and nanosafety. He has pioneered research in design and surface engineering of nanoparticles and functional nanosystems for parenteral site-specific targeting, drug delivery and imaging modalities, as well as the molecular basis of nanomaterial/polymer immune toxicity and cytotoxicity.

Presentation Title

Integrative nanomedicine: phage-derived peptidic assemblies for therapeutic nucleic acid delivery  targeting  two  receptors

Summary
  • Demonstration of a phage-derived peptidic self-assembly targeting two receptors in different geometries
  • Peptide complexation with siRNA forming different geometries depending on siRNA structure
  • Functional delivery of siRNA to target cells with unprecedented safety
  • In vivo proof of targeting

Udi QIMRON, PhD

Professor, Tel Aviv University, Israel

Dr. Qimron’s lab studies the interactions between bacteria and their viruses, the bacteriophages. Their studies are focused on the bacterial immune system against bacteriophages, the CRISPR-Cas system. Dr. Qimron’s lab pioneered studies on how the CRISPR-Cas system samples small DNA segments from bacteriophages to memorize them. His group was the first to demonstrate that two enzymes mediate this activity and showed the minimal genetic requirements for this memorization process. In collaboration with Dr. Sorek’s group from Weizmann Institute of Science, Israel, his group also recently revealed how self-memorization (and consequently autoimmunity) against the bacterial genome is prevented in the CRISPR-Cas immune system. In addition, Dr. Qimron’s group recently showed that the CRISPR-Cas system can be used as a new tool to selectively target antibiotic resistant bacteria.

Dr. Udi Qimron earned his Ph.D. (direct track) in Biology from Ben Gurion University, Israel, in 2004. He conducted his post-doctoral studies in the lab of Dr. Charles C. Richardson, at Harvard Medical School from 2004 to 2009. In 2009 he established his lab in the Medical School of Tel Aviv University, Israel, and was appointed to an associate professor in 2013.

Dr. Qimron studies are published in high-profile journals. He recently won the prestigious €1.5M European Research Council grant, and received the prestigious Bergmann award for an outstanding grant proposal.

Presentation Title

CRISPR/Cas-encoding bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria

Summary

The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. I will present two studies, both based on a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. The strategy uses temperate phages to deliver sensitizing DNA cassettes into the genome of antibiotic-resistant bacteria. The delivered cassettes neutralize antibiotic resistance-conferring plasmids and provides a selective advantage. This linkage between antibiotic-sensitization and a selective advantage allows killing of only antibiotic-resistant bacteria while protecting antibiotic-sensitized bacteria. Phages designed according to this strategy may be used in animal husbandries, hospital surfaces and hand-sanitizers to facilitate replacement of antibiotic-resistant pathogens with sensitive ones.

Nikolaus RAJEWSKY, PhD

Professor, Max Delbrück Center for Molecular Medicine, Germany

Nikolaus Rajewsky earned his Ph.D. in Theoretical Physics at the University of Cologne, Germany (1997). After a postdoctoral period at Rutgers University and at Rockefeller University, he was an “Assistant Professor for Biology and Mathematics” in the Department of Biology at New York University (2003-2006). In 2006 he became a full Professor at the Charite and the Max Delbruck Center for Molecular Medicine in the Helmholtz Association in Berlin, Germany. He conceived and directs the “Berlin Institute for Medical Systems Biology” (BIMSB). BIMSB is a new branch of the MDC and will grow to a size of ~25 PIs in downtown Berlin.

Nikolaus Rajewsky uses both computational and experimental molecular biology methods to study gene regulation in animals. A focus of his work is on the function and mechanisms of small non-coding RNAs and RNA binding proteins in development and stem cells. Nikolaus’ research has been cited over 13,000 times and has been featured in numerous high-ranking scientific journals and in the press. His latest awards include: IUBMB medal, FEBS award, “Berliner Wissenschaftspreis”, EMBO membership, and in 2012 the highest award for research in Germany, the “Leibniz Preis” of the DFG. Since 2008 he is also a “Global Distinguished Professor of Biology at New York University” and in 2014 has received on honorary PhD in Human Biology and Medical Genetics by Sapienza University of Rome, Italy.

Presentation Title

Regulatory RNAs

Summary

I will summarize our current efforts to understand more about circular RNAs (circRNAs). Recently, circRNAs (single-stranded covalently closed RNAs) have been reported to be widely and dynamically expressed during animal development. We have found that circRNAs are particularly highly expressed in neuronal cells and some other human tissues. I will report out latest insights into circRNAs biogenesis and function.

Laura SEPP-LORENZINO, PhD

Vice President, Entrepreneur in Residence, Alnylam Pharmaceuticals, USA

Dr. Sepp-Lorenzino joined Alnylam in 2014. Before joining Alnylam, Dr. Sepp-Lorenzino spent 14 years at Merck & Co., having most recently served as Executive Director and Department Head, RNA Therapeutics Discovery Biology. In this role, she was responsible for identification and optimization of siRNAs and delivery vehicles, advancement of pre-clinical candidates, and development of an siRNA-conjugate platform to expand the repertoire of tissues accessible to in vivo siRNA delivery. Prior to RNAi, Laura worked in oncology drug discovery and development, having led the Cancer Research Department at Merck West Point, and having been an Assistant Lab Member at Memorial Sloan-Kettering Cancer Center. Laura received her Professional Degree in Biochemistry from the University of Buenos Aires, and her M.S. and Ph.D. in Biochemistry from New York University.

Presentation Title

Hepatocyte targeted RNAi Therapeutics: case studies in rare diseases and hepatitis B

Summary
RNA interference is an endogenous cellular mechanism for controlling gene expression in which small interfering RNAs (siRNAs) bind RNA-induced silencing complex (RISC) to mediate the cleavage of target mRNA. Conjugation of siRNA to an asialoglycoprotein receptor ligand derived from N-acetylgalactosamine (GalNAc) facilitates targeted delivery to hepatocytes and silencing of target mRNAs in vitro and in vivo after subcutaneous (SC) administration. Enhanced stabilization chemistry (ESC) of siRNA results in improved potency and duration of action, enabling infrequent, low volume dosing (Nair et al. J. Am. Chem. Soc., 2014). This delivery platform is being employed in several of Alnylam’s programs, including programs in clinical development. Case studies highlighting preclinical to clinical translation will be presented for genetic medicine programs in TTR-Amyloidosis, Hemophilia and Rare Bleeding Disorders, Hepatic Porphirias and Complement-Mediated Diseases. Lastly, the ESC GalNAc RNAi therapeutic platform is being applied to the identification and development of ALN-HBV for the treatment of chronic hepatitis B.

Thomas A. STEITZ, PhD

Professor, Yale University, USA

Howard Hughes Medical Institute

National Academy of Sciences

2009 Nobel Prize in Chemistry

Thomas A. Steitz is Sterling Professor of Molecular Biophysics and Biochemistry and Professor of Chemistry at Yale University as well as an Investigator of the Howard Hughes Medical Institute. He received a B.A. degree in chemistry from Lawrence University and a Ph.D. degree in molecular biology and biochemistry from Harvard. After postdoctoral research at the MRC Laboratory in Cambridge, England he joined the Yale faculty. He is a member of the U.S. National Academy of Sciences, the American Academy of Arts and Sciences and a Foreign Member of the Royal Society. He has received numerous prizes including the Keio Medical Science Prize, the Gairdner International Award and the 2009 Nobel Prize in Chemistry.

For the last three decades, research in the laboratory of Dr. Steitz has focused on obtaining structural insights into the molecular mechanisms by which the proteins and nucleic acids involved in the central dogma of molecular biology carry out gene expression from replication and recombination of the DNA genome to its transcription into mRNA followed by the various components associated with the translation of mRNA into protein. Perhaps the most significant insights have been derived from the atomic structure of the large ribosomal subunit, which proved that the ribosomal RNA is entirely responsible for catalyzing peptide bond formation and provided insights into how this mammoth RNA assembly is folded and functions as an enzyme. Most recently, research has focused on the structures of the 70S ribosome in complex with factors involved in various steps of the protein synthesis process. The many structures of the large subunit complexed with various different antibiotics determined at Yale have identified numerous different antibiotic binding sites near the site of protein synthesis.

Presentation Title

From the structure and function of the ribosome to new antibiotics

Summary
To expand our understanding on how the ribosome functions in the various steps of protein synthesis, we have determined the structures of the 70S ribosome bound to several protein factors captured in different steps of the process. Our structure of the 70S ribosome bound to elongation factor G (EF-G) captured in a compact state of EF-G and three tRNA molecules provides insights into how EF-G promotes translocation. Our structures of many complexes of the 50S and 70S ribosomes with antibiotics show how they inhibit protein synthesis, how mutations make them resistant to antibiotics and how new antibiotics can be developed. Recently, we have shown how an oligopeptide binds in the ribosome peptide tunnel and can inhibit protein synthesis.

Jack W. SZOSTAK, PhD

Professor, Harvard Medical School, USA

Howard Hughes Medical Institute

National Academy of Sciences

2009 Nobel Prize in Physiology or Medicine

Dr. Szostak received his B.Sc. from McGill University in Montreal in 1972, and then conducted his graduate research under the supervision of Prof. Ray Wu at Cornell University, Ithaca, NY, obtaining his Ph.D. in 1977. Dr. Szostak then moved to the Sidney Farber Cancer Institute and Harvard Medical School in 1979, and then to Massachusetts General Hospital in 1984. During the 1980s he carried out research on the genetics and biochemistry of DNA recombination, which led to the double-strand-break repair model for meiotic recombination. At the same time Dr. Szostak made fundamental contributions to our understanding of telomere structure and function, and the role of telomere maintenance in preventing cellular senescence. For this work Dr. Szostak shared, with Drs. Elizabeth Blackburn and Carol Greider, the 2006 Albert Lasker Basic Medical Research Award and the 2009 Nobel Prize in Physiology or Medicine. In the 1990s Dr. Szostak and his colleagues developed in vitro selection as a tool for the isolation of functional RNA, DNA and protein molecules from large pools of random sequences. His laboratory used in vitro selection and directed evolution to isolate and characterize numerous nucleic acid sequences with specific ligand binding and catalytic properties. From 2000 until the present Dr. Szostak’s research interests have focused on the laboratory synthesis of self-replicating systems and the origin of life.

Presentation Title

The origins of cellular life

Summary

The earliest living cells must have had very simple structures in order to emerge spontaneously from the chemistry of the early earth. We are attempting to synthesize such simple artificial cells in order to discover plausible pathways for the transition from chemistry to biology. Very primitive cells may have consisted of a self-replicating nucleic acid genome, encapsulated by a self-replicating cell membrane. We have recently described robust pathways for the coupled growth and division of primitive cell membranes composed of fatty acids, which were likely to have been available prebiotically. However, no process for the replication of a nucleic acid genome, independent of evolved enzymatic machinery, has yet been described. I will discuss our recent progress towards the realization of an efficient and accurate system for the chemical replication of RNA.

Zhou SONGYANG, PhD

Professor, Baylor College of Medicine, USA

Professor, Sun Yat-sen University, China

ProfessionalExperience

1995             Ph.D.in Molecular Physiology, Tufts University, USA.

1995-1996  Postdoctoral Fellow, Harvard University,Cambridge, MA.

1996-1998  PostdoctoralFellow, Massachusetts Institute of Technology, Cambridge.

1998-2007  Assistant and Associate Professor, Departmentof Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX

2008-            Professor, Department of Biochemistry andMolecular Biology, Baylor College of Medicine, Houston, TX

2009-            Director, SYSU-Baylor College of MedicineJoint Research Center for Biomedical Sciences, School of Life Sciences, SYSU,Guangzhou

Honors

1995             Scientist  Most cited paper of the year (Mol. Cell.Biol. 14, 2777-85.)

1996-1998   Irvington Institute PostdoctoralFellowship

1999-2003   EllisonNew Scholar

2004             Article selected as one of 30 mostmemorable papers in 30-year history of the journal Cell (Cell, 72, 767-778)

2006             LLS scholar

2007             Michael Debakey Excellence of Research Award

Dr. Songyang is interested inthe molecular mechanisms that regulate cell survival, genome stability, stemcell pluripotency, and cancer initiation through proteomic and functionalgenomic approaches.  Dr. Songyang’s majorresearch areas include telomeres and telomerase, DNA damage repair signaling,and embryonic stem cell self-renewal and differentiation.  Dr. Songyang has also developed severaltechnology platforms to study protein-protein interactions and signalingpathways. He has published more than 110 papers in leading journals such asNature, Science, Cell, Nature Cell Biology, NSMB, Molecular Cell, PNAS, Curr.Biol., and JCB.  His publications werecited more than 11,000 times.

Presentation Title

GeneEditing in mouse and human cells

Summary
Gene-modifiedhuman cells and mice are important tools for studying gene function in vivo. Before 2010, gene-modified humancells and mice were mainly generated by gene targeting, which was time-consumingand technique-intensive. In 2010, artificial nucleases based genome-editingtools were developed to facilitate genetic modified human cells and miceproduction. After introduced into cells, these artificial nucleases can inducedouble strand break (DSB) at target sites. DSBs will be repaired by non-homologousend joining (NHEJ) or homology directed repair (HDR), resulting in frame-shiftmutation or precise gene modification respectively. Genome editing in mouseembryos provides an easier and more efficient way to generate mutant mice. Sofar, several different kinds of artificial nucleases have been developed,including ZFN, TALEN and CRISPR/Cas systems. The application of CRISPR/Castechnology for genetic studies in human cells and mice will be discussed here.

Michael P. TERNS, PhD

Professor, University of Georgia, USA

Dr. Michael Terns has a long-standing scientific interest in understanding non-coding RNA biology. Among his many accomplishments, Terns’ work has revealed the pathways that regulate the activity of telomerase, an enzyme that is essential to the development of most cancers. His research group has studied extensively the C/D and H/ACA small nucleolar RNPs, enzymes that build and support critical cellular machinery, which has provided key insights into the development of the fatal bone marrow disease dyskeratosis congenita and a common neuromuscular disease called spinal muscular atrophy. Most recently, Terns has conducted groundbreaking research into CRISPR-Cas systems, small RNA-based immune systems that protect bacteria from viruses and other threats. These systems are being employed as versatile genome editing tools and novel gene-knockdown platforms among other important biotechnological and biomedical applications.

Dr. Terns received his BS in Biochemistry from the University of Michigan in 1985 and his PhD from Pennsylvania State University in 1990 with Samson Jacob, where he studied mechanisms of pre-mRNA polyadenylation. He did his postdoctoral training at the University of Wisconsin in the laboratory of James Dahlberg, studying intracellular trafficking of small nuclear RNAs. Dr. Terns became a principal investigator in 1995 at The University of Georgia where he continues to carry out his research. He is an American Cancer Society Research Scholar and Distinguished Research Professor.

Additional information about Dr. Terns can be found in the following sites:

http://www.bmb.uga.edu/rterns/index.html

http://www.genetics.uga.edu/directory/michael-terns

Presentation Title

CRISPR-Cas: small RNA mediated prokaryotic immune systems

Summary
CRISPR-Cas systems are RNA-based immune systems that control invasions of viruses and plasmids in archaea and bacteria. Prokaryotes with CRISPR-Cas immune systems capture short invader sequences within the CRISPR loci in their genomes, and small RNAs produced from the CRISPR loci (CRISPR (cr)RNAs) guide Cas proteins to recognize and degrade the invading nucleic acids. There are multiple variations of the pathway found among prokaryotes, each mediated by largely distinct components and mechanisms that we are only beginning to understand. Using the hyperthermophile Pyrococcus furiosus, we have delineated several key steps in CRISPR-Cas invader defense pathways. Evidence will be presented that P. furiosus employs an impressive arsenal of three co-existing distinct immune systems, which collectively target invaders at both the RNA and DNA levels to provide robust protection from diverse invaders.

 

Takanori YOKOTA, MD, PhD

Professor, Tokyo Medical and Dental University, Japan

Takanori Yokota received Japanese National License of Medical Doctors in 1984 and the Ph.D. degree from Tokyo Medical and Dental University,Tokyo, Japan, in 1990.

From 1984, he served as a Neurologist at Tokyo Medical and Dental University ;

from 1998, as a Research Fellow in Bredesen’s lab in Burham Institute (CA, USA);

from 1999, as a Research Fellow in Bredesen’s lab in Buck Center for Aging Research (CA, USA);

from 2000, as a Assistant Professor in Neurology at Tokyo Medical and Dental University;

2004, as a Associate Professor in Neurology at Tokyo Medical and Dental University.

From2010 to the present, he serves as a Professor in Neurology at Tokyo Medical andDental University.

His major interest includes gene therapy of neurological diseases.

Dr. Yokota is a scientific board of Oligonucleotide Therapy Society (OTS)

 

Award:

2001 Award of 42nd Japananese Neurological Association
2003 Award of 31th Japananese the Naito memorial Foundation
2003 Award of 56th Japananese Vitamin Association

2006 Award of 20th Meeting of Japanese Society of Neuroimmunology

Presentation Title

DNA/RNA heteroduplex oligonucleotide – a novel concept of therapeutic oligonucleotides

Summary
Antisense oligonucleotides (ASOs) are recognized therapeutic agents for the modulation of specific genes at the post-transcriptional level. Similar to any medical drugs, there are opportunities to improve their efficacy and safety. Here we develop a short DNA/RNA heteroduplex oligonucleotide (HDO) with a structure different from double-stranded RNA used for short interfering RNA and single-stranded DNA used for ASO. A DNA/locked nucleotide acid gapmer duplex with an α-tocopherol-conjugated complementary RNA (Toc-HDO) is significantly more potent at reducing the expression of the targeted mRNA in liver compared with the parent single-stranded gapmer ASO. Toc-HDO also improves the phenotype in disease models more effectively. In addition, the high potency of Toc-HDO results in a reduction of liver dysfunction observed in the parent ASO at a similar silencing effect. HDO technology offers a novel concept of therapeutic oligonucleotides, and the development of this molecular design opens a new therapeutic field.

       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。