Lifetime Achievement Award

Given the COVID-19 pandemic and the impossibility to meet in person, OTS will award two Lifetime Achievement Awards in 2021, to Dr. Ryszard Kole and Dr. Frank Bennett. Both will give their award lecture at the 2021 meeting. The Award Committee feels it is fitting to have these individuals as a ‘double bill’. Not only have both made important contributions to basic science, both were also instrumental in the development of antisense oligonucleotide drugs that modulate splicing to correct severe genetic disease. We look forward to the 2021 OTS meeting as a celebration of Dr. Kole and Dr. Bennett.

Ryszard Kole, PhD
Ryszard Kole, PhD, Ercole Consulting

Dr. Kole received his Ph.D. degree from the Institute of Biochemistry and Biophysics, Polish Academy of Sciences, in Warsaw where he studied RNA the role of ribonucleases in cell function. He continued this line of work at Yale, in the Departments of Biology and Human Genetics, and during his 25-year tenure as Professor of Pharmacology at the UNC Chapel Hill. Dr. Kole’s activities span the gamut from biochemical assays, cell culture and animal studies to clinical trials as well as to methods of oligonucleotide delivery and improvements in oligonucleotide chemistry. Dr. Kole’s primary discovery was that pre-mRNA splicing provided a novel target for sequence specific therapies of severe disorders such as thalassemia, cystic fibrosis, DMD as well as cancer, inflammatory and metabolic disorders. It also represented a novel technology of oligonucleotide induced modulation of pre-mRNA splicing and exon skipping. [Dominski & Kole (1993) PMID: 8378346). His approach has huge therapeutic potential since over 90% of human genes produce alternatively spliced mRNA and about 50% of genetic disorders are caused by errors in pre-mRNA splicing. To commercially exploit this fertile field Dr. Kole founded Ercole Biotech, a company, which together with his group at UNC provided proof of concept in models of several rare diseases. In 2008 Ercole was acquired by Sarepta Therapeutics (previously AVI Biopharma), a Cambridge, MA company. At AVI and Sarepta Dr. Kole served as SVP Discovery and Distinguished Scientist. He is now a consultant to Sarepta. Sarepta’s breakthrough drug for DMD, (Exondys 51), approved by FDA 09/1/2016, is a direct result of Dr. Kole’s pioneering discoveries in oligonucleotide-induced modulation of pre-mRNA splicing. Dr. Kole’s approach was also explored by other researchers and companies some less (Glaxo/Prosensa) some more successfully (Spinraza, approved by FDA, 23/12/2016).

C. Frank Bennett
C. Frank Bennett, PhD, Executive Vice President, Chief Scientific Officer, Ionis Pharmaceuticals

Dr. Bennett is the executive vice president and chief scientific officer at Ionis Pharmaceuticals and one of the founding members of the company. He is responsible for continuing to advance antisense technology and expanding Ionis drug discovery platform. Dr. Bennett is also the franchise leader for neurological programs at Ionis. He has been involved in the development of antisense oligonucleotides as therapeutic agents, including research on the application of oligonucleotides for inflammatory, neurodegenerative diseases and cancer, oligonucleotide delivery, pharmacokinetics and medicinal chemistry.

Dr. Bennet is a co-recipient of the 2019 Breakthrough Prize in Life Sciences for his contributions to the discovery and development of SPINRAZA® (nusinersen) and the 2018 Hereditary Disease Foundation’s (HDF) Leslie Gehry Brenner Prize for Innovation in Science for his leadership and continued commitment to developing antisense therapies for Huntington’s disease (HD).

Dr. Bennett has published more than 230 papers in the field of antisense research and development, and he is an inventor on more than 175 issued patents.

Prior to joining Ionis, Dr. Bennett was associate senior investigator in the Department of Molecular Pharmacology at SmithKline and French Laboratories (currently, GlaxoSmithKline).

He received his Ph.D. in Pharmacology from Baylor College of Medicine, Houston, Texas and his B.S. degree in Pharmacy from the University of New Mexico, Albuquerque, New Mexico. He performed his postdoctoral research in the Department of Molecular Pharmacology at SmithKline and French Laboratories.

Dr. Bennett serves on the Advisory Board for the Hereditary Disease Foundation.

Dr. Alan M. Gewirtz Memorial Scholarship Award for Graduate Students

Chantal M. Ferguson, RNA Therapeutics Institute, University of Massachusetts Medical School

RNAi modulation of APOE as a potential therapeutic for Alzheimer Disease

Chantal joined the Khvorova Lab in 2017 with an interest in developing new tools to understand and treat neurological disorders. Her thesis work aims to understand the spatial and functional relationship between brain and liver Apolipoprotein E and their impact on the Alzheimer disease pathogenesis. Using chemically modified siRNAs, Chantal aims to identify hyper functional siRNAs that modulate the expression of genes associated with the onset of Alzheimer disease (ApoE, Tau, SNCA) in rodent and large animal models. The ability to modulate the expression of disease related genes in the rodent and non-human primate brain allows us to investigate their role in brain function, aging, and disease in the context of a living brain, and provides opportunities for the development of novel therapeutics.

Dr. Alan M. Gewirtz Memorial Scholarship Award for Postdoctoral Fellows and Junior Industrial Professionals

Annabelle Biscans, PhD, AstraZeneca

Designing New Chemically Engineered siRNAs for Extrahepatic Delivery

Annabelle Biscans obtained her PhD in chemistry from the University of Montpellier (France) in 2015, where her work focused on the chemical synthesis of RNA prodrugs for the development of new therapeutic oligonucleotides. During her PhD, she established and optimized synthetic methods to successfully synthesize novel 2’-modified siRNAs and demonstrated that incorporation of 2’-biolabile moieties can be efficiently used to improve siRNA stability and uptake without major toxicity. To further pursue her interest and contribute to the oligonucleotide therapeutic field, Annabelle joined Prof. Anastasia Khvorova’s lab in the RNA Therapeutics Institute at the University of Massachusetts Medical School as a postdoctoral associate in 2016. There, she made major contributions to the development of novel chemistries for improving the delivery and uptake of oligonucleotide therapeutics. She was able to design and identify novel conjugated siRNAs that enable safe and robust silencing in various extra-hepatic tissues including muscle, heart, and lung. This crucial discovery allows for the targeting of several new targets for therapeutic intervention. Recently, Annabelle joined the oligonucleotide team at AstraZeneca as an Associate Principal Scientist to further help advancing oligonucleotide therapeutic technologies.

Mary Ann Liebert publishers, Inc. Young Investigator Award

Maja M. Janas De Angelis, PhD

Advancing the Safety and Reach of RNAi Therapeutics

Maja Janas De Angelis, PhD, DABT is currently an Associate Director, Investigative Toxicology, at Alnylam Pharmaceuticals. She earned her Bachelor of Arts in Chemistry and Biochemistry from the University of Colorado in 2007, and her PhD in Biological and Biomedical Sciences from Harvard University in 2012, working with Dr. Carl D. Novina on novel regulators of microRNA biogenesis and function. After completing her PhD, Dr. Janas De Angelis accepted a position as Presidential Postdoctoral Fellow in the RNAi Therapeutics group at Novartis Institutes for BioMedical Research, working on mechanisms of selective microRNA export via exosomes and novel roles of double-stranded RNA binding proteins in microRNA and siRNA pathways. In 2014, Dr. Janas De Angelis joined the Investigative Toxicology group at Alnylam Pharmaceuticals, where she is championing a variety of investigative, molecular mechanism-based research efforts related to preclinical safety evaluation and CNS targeting of RNAi therapeutics.

Paper of the Year Winners

July 2019 – June 2020

Congratulations to the Winner of the OTS Paper of the Year Award!

The Paper of the Year Award is designed to honor the most impactful papers in the field of oligonucleotide therapeutics.

In 2020, the OTS introduced two categories for Paper of the Year award, the Basic Research and Late Discovery categories.  This change reflects the scope of excellent research being done in the field of oligonucleotide therapeutics.

Below are the details for each award.

Basic Paper Of The Year Award – Winners

This year, OTS has awarded three winners in the Paper of the Year – Basic Science category. They reveal that, contrary to expectations, gapmer antisense oligonucleotides that target noncoding transcripts can affect transcription. This conclusion affects how ASOs are used as tools to study noncoding RNAs and suggests a more complex relationship between noncoding RNAs and gene transcription.

For more detailed information on these three papers, click here. 

Directed RNase H cleavage of nascent transcripts causes transcription termination
Lai F, Damle SS, Ling KK, Rigo F.

Frank Rigo, PhD

In 2002, I completed my undergraduate studies in molecular biology and biochemistry at Marquette University. From 2002-08, I earned my Ph.D. at UCLA in the Biochemistry Department under Harold Martinson. There, I dissected the mechanistic basis for how splicing and polyadenylation are interconnected with transcription. After earning my Ph.D. in 2008, I pursued a post-doc in industry at Ionis Pharmaceuticals under Frank Bennett. During my two-year post-doc, I focused on developing a therapy for spinal muscular atrophy based on ASO-mediated splicing correction of SMN2. The ASO (Spinraza) that I helped develop was approved by the US FDA in 2016. In 2010, I continued my career at Ionis. Early on, I lead the efforts to advance ASO technology by identifying therapeutic targets amenable to ASO-mediated splicing modulation. Now I lead functional genomics and exploratory drug discovery at Ionis. I have published over 100 articles in the fields of RNA biology, antisense technology and neuroscience.

Antisense-mediated transcript knockdown triggers premature transcription termination
Dr. Joshua Mendell, Dr. Jong-Sun Lee

Dr. Joshua Mendell is a Professor of Molecular Biology at UT Southwestern Medical Center and an Investigator of the Howard Hughes Medical Institute. His laboratory investigates broad questions in RNA biology, including the mechanism and physiologic roles of post-transcriptional regulatory pathways, the regulation and function of various classes of noncoding RNAs, such as microRNAs and long noncoding RNAs, and the contribution of altered RNA regulation and function to diseases such as cancer.

Dr. Jong-Sun Lee is a postdoctoral fellow in the Mendell laboratory. He obtained a B.S. in Biology from Baylor University in 2008 and a Ph.D. in Biomedical Science from the Mayo Clinic in 2016. During his graduate training in the laboratory of Dr. Zhiguo Zhang, Dr. Lee discovered a new role for the O-GlcNAc modification in nucleosome assembly (Lee et al., PNAS, 2016) and studied the role of the nucleosome regulator Pak2 in senescence and aging (Lee et al., PNAS, 2019).

A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes
Eaton JD, Francis L, Davidson L, West S.

Steve West did his PhD at Oxford University in Prof Nick Proudfoot’s lab. It was here that he developed a strong interest in understanding mechanisms of transcriptional termination. After remaining in Oxford for a post-doc, he obtained an independent fellowship from The Wellcome Trust to establish his research group in Edinburgh where his lab’s focus remained on transcription and RNA metabolism. Following a short stint at The University of Sheffield, the lab relocated to Exeter to join the newly established Living Systems Institute where his research into transcriptional mechanisms continues to be funded by The Wellcome Trust.

Josh Eaton was an undergraduate at The University of Sheffield, after which he joined Steve’s lab as a PhD student funded by The Lister Institute before relocating to Exeter. Josh’s PhD work has focused on establishing CRISPR/Cas9 genome-editing as a means to study RNA metabolic factors and combining this with transcriptome-wide mapping of transcription. This interest lead to the hypothesis that 5’ phosphate-containing cleavage products might promote transcriptional termination irrespective of the mechanism that generated them. The finding that RNaseH1-directed RNA cleavage indeed promoted transcriptional termination confirmed this and in part lead to the paper that we are pleased has been nominated by the OTS.

Late Discovery Paper Of The Year Award – Winners

This year, OTS has awarded two winners in the Paper of the Year – Late Discovery category. In both cases the research examined the effect of inclisiran, which is a small interfering RNA, on LDL cholesterol levels in patients with heterozygous familial hypercholesterolemia (Raal et al., 2020), or atherosclerotic cardiovascular disease (Ray et al., 2020), and reported significant reductions in levels of patients compared to controls.

To read more about these two papers, click here.

Inclisiran for the treatment of heterozygous familial hyper-cholesterolemia
Raal FJ, Kallend D, Ray KK, Turner T, Koenig W, Wright RS, Wijngaard PLJ, Curcio D, Jaros MJ, Leiter LA, Kastelein JJP; ORION-9 Investigators.

Frank Rigo, PhD

MBBCh, FRCP, FRCPC, FCP(SA), Cert Endo, MMED, PhD

Director, Carbohydrate & Lipid Metabolism Research Unit

Professor & Head, Division of Endocrinology & Metabolism, University of the Witwatersrand

email: frederick.raal@wits.ac.za

Professor Derick Raal is currently Professor and Head of the Division of Endocrinology and Metabolism, as well as Director of the Carbohydrate and Lipid Metabolism Research Unit, University of the Witwatersrand, Johannesburg, South Africa. After obtaining his MBBCh degree cum laude in 1981 he completed his registrarship in Internal Medicine and obtained his MRCP(UK) and FCP(SA) in 1987, his Master of Medicine in 1991, his FRCP(Canada) in 1995 and the FRCP(UK) in 2000. He sub-specialized in Endocrinology & Metabolism and was awarded his PhD on studies in patients with familial hypercholesterolaemia in June 2000. Professor Raal has received numerous postgraduate awards including the Jack Gear memorial award for medical registrars, the TH Bothwell Research Prize in 2000, the FJ Milne award in 2013 and the University of the Witwatersrand Vice Chancellor’s Research Award in 2015. He is a past chairperson and secretary of the Society of Endocrinology, Metabolism and Diabetes of Southern Africa (SEMDSA) and has been the secretary of the Lipid and Atherosclerosis Society of Southern Africa (LASSA) since its inception in 1989.

He has authored or co-authored over 250 original articles and book chapters and has reviewed for several international journals including the New England Journal of Medicine, the Lancet, Circulation, the American Journal of Cardiology, Diabetes Care, Atherosclerosis, and Arteriosclerosis, Thrombosis and Vascular Biology. He is also on the Editorial Board of Atherosclerosis. He is a member of several scientific societies including the International Atherosclerosis Society, the European Atherosclerosis Society and the American Heart Association.

Professor Raal is particularly interested in lipids and lipid disorders and has been integrally involved in the management of familial dyslipidaemia, particularly heterozygous and homozygous familial hypercholesterolaemia (FH). His Unit has one of the largest cohorts, if not the largest cohort, of homozygous FH patients in the world and has contributed, and continues to contribute, to the management of these unfortunate patients. The major focus of his research remains the clinical, biochemical, genetic and therapeutic management of this condition and he continues to conduct studies with novel therapies such as anti-sense apo B-100, PCSK9-inhibitors and ANGPTL3-inhibitors in this patient group.

He is also a keen sportsman and has been awarded provincial colours for both tennis and squash.

Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol
Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP; ORION-10 and ORION-11 Investigators.

Kausik Ray

Kausik Ray is currently Professor of Public Health, Deputy Director of Imperial Clinical Trials Unit and Head of Commercial Trials within the Department of Public Health and Primary Care, School of Public Health, Imperial College London, Consultant Cardiologist and Chief Clinical Officer and Head of Trials – Discover Now as well as NIHR ARC National Lead of Cardiovascular Disease.

Professor Ray received his medical education (MB ChB, 1991) at the University of Birmingham Medical School, his MD (2004) at the University of Sheffield, a postdoctoral fellowship at Harvard Medical School and finally an MPhil in epidemiology (2007) from the University of Cambridge.

A Fellow of the American College of Cardiology, the European Society of Cardiology, the American Heart Association and the Royal College of Physicians, Kausik Ray is also a member of the British Cardiovascular Society and President-Elect of the European Atherosclerosis Society, also serving on the EAS Consensus panel and EAS Executive Committee. Professor Ray has either been the National Lead Investigator, Principal Investigator, or served on committees for several major medical trials, as well as international registries and is currently involved in 8 ongoing trials in lipids and diabetes and the PI for ORION 1, 3, 11 assessing PCSK9 inhibition through RNA interference and BETONMACE assessing BET protein inhibition in patients with ACS.

Professor Ray’s research interests have focused on the prevention of coronary disease with a focus on lipids, diabetes, biomarkers and risk prediction. He has an H index of 80, an i10 of 199 and over 82,000 citations for his work in journals such as New England Journal of Medicine, The Lancet, JAMA, European Heart Journal, Circulation and JACC.

Key original contributions which have influenced European and American guidelines include demonstrating the early benefits of statin therapy post ACS, the impact of more/less intensive glycaemic control on CVD and the risks/benefits of aspirin therapy in primary prevention. Recently, his work on statins and diabetes risk led to a global label change for statins by the FDA and EMEA. Currently Professor Ray leads the EAS FH Studies collaboration which is the first global registry of FH which includes 70
countries and 61,000 cases, as well as being the Senior PI for the TOGETHER study looking at cardiometabolic risk in the vascular health checks in 250,000 people in London.