Dr. Alan M. Gewirtz Memorial Scholarship – Graduate Students
Mr. Hassan Fakih
Department of Chemistry, McGill University
Hassan obtained his bachelor’s degree in chemistry from the American University of Beirut in 2016. Then, he Joined the Sleiman Lab at the Chemistry department of McGill University to pursue his doctorate degree. His work is focused on the biomedical applications DNA nanocarriers, specifically on designing and testing DNA-based nanocarriers for the delivery of nucleic acid therapeutics with characteristics that enable them to move faster into clinical trials (cost effective, biocompatible, specificity, stability etc.). His work resulted in producing simple yet effective sequence-controlled nucleic acid-polymer conjugates that assemble into spherical nucleic acids (SNAs) with stimuli responsive activation, as well as FANA modified-SNAs that show promising results of efficacy without any transfection agents. He also is working on developing and studying conjugates that control the protein corona that forms arounds therapeutics in vivo and impact their pharmacokinetics/dynamics. Outside of research, Hassan is very interested in scientific communication and bridging science with policy and management.
Dr. Alan M. Gewirtz Memorial Scholarship – Postdoctoral Fellows and Junior Industrial Professionals
Kotaro Yoshioka, MD, PhD
Department of Neurology and Neurological Science, Tokyo Medical and Dental University
Kotaro Yoshioka received his PhD in 2016 from Tokyo Medical and Dental University (Japan), where he has developed a unique double-stranded ASO technology, “Heteroduplex oligonucleotide (HDO)” in the laboratory of Takanori Yokota. His work revealed that new type of HDO for antimiR can silence the target microRNA in vivo more efficiently than the original single-stranded antimiR with a novel intracellular mechanism. To further pursue a potent therapeutic oligonucleotides targeting extrahepatic tissues, especially CNS, he has developed a novel neuroactive double-stranded ASO, overhanging duplex oligonucleotide (ODO), that enables highly efficient delivery not only to multiple tissues such as skeletal muscles, peripheral lymphocytes and intestines via systemic injections, but also to brain via intraventricular injection. In addition, his postdoctoral work revealed an additional carrier protein of ODO, transferrin and a unique cellular uptake pathway associated with transferrin-receptor. Moreover, this double-stranded HDO-technology via CSF route enables significant improvements of CNS-toxicities of ASO and increases therapeutic index in mice and cynomolgus monkeys. These crucial discoveries by Dr. Yoshioka allow for the regulating new type of target gene and tissues more efficiently and safely, especially in CNS by the new double-stranded oligonucleotides technology.
Mary Ann Liebert, Inc. publishers Young Investigator Award
Alex Garanto, PhD
Radboud university medical center (Radboudumc)
Dr. Alejandro (Alex) Garanto is currently an Assistant Professor at the Departments of Pediatrics and Human Genetics of the Radboudumc in Nijmegen (the Netherlands). He obtained his PhD from the University of Barcelona in 2011 under the supervision of Prof. Gonzàlez-Duarte and Prof. Marfany. After a short postdoc with Prof. Marfany at the University of Barcelona, Alex moved to the Netherlands to start working with Prof. Collin on the design and characterization of antisense oligonucleotides (ASOs) as a potential approach to treat inherited retinal diseases. The first target was an intronic mutation in CEP290, and part of this preclinical work led to a clinical trial, which is currently in phase 3. Furthermore, he and his colleagues expanded the use of ASOs to correct splicing defects in other retinal disease-associated genes, such as CHM and ABCA4. Especially for ABCA4, more than 25 splicing defects caused by (deep-)intronic variants have been successfully corrected using ASOs and currently, some of these ASOs are being further characterized for clinical application. Since 2020, he is recognized as a group leader at the Radboudumc and his research focuses on the development of molecular therapies, mainly using RNA-based approaches, for inherited neurometabolic diseases and inherited retinal diseases.
2021 Paper of the Year Winners
Paper of the Year – Basic
Givosiran, a GalNAc-conjugated siRNA, which was recently approved on the market, displays sustained knock-down over month-long periods. The following paper investigates the reasons behind those impressive pharmacodynamic properties. After looking into various mechanisms related to stability, accumulation or entrapment, the authors conclude that the GalNAc-conjugated siRNAs can be retained in acidic intracellular compartments from where they get slowly released. Upon delivery to the cytosol, the drug can exhibit its therapeutic activity by loading into RISC. Results are also compared to LNPs loaded siRNAs. The increased half-life in these acidic organelles was revealed to account for most of the long-term activity of the therapeutic. The paper exposed a major factor of the mechanism of action of conjugated siRNAs.
Papers of the Year - Late Discovery
The need for platforms to develop vaccines rapidly and efficiently was clearly highlighted by the Covid-19 pandemic. The first vaccine against SARS-CoV-2 was approved only a few months after the beginning of the global health threat and is now being rolled out over the world. Interestingly, the two first approved vaccines were both mRNA-based, which was also a premiere for the field. The two papers herein highlight this milestone, as the first clinical reports on mRNA-1273 and BNT162b1 (respectively Moderna and Pfizer/BioNtech vaccines). They revealed the results of Phase I/II studies (first in humans) of each vaccine respectively. In both cases, the authors reported effective therapeutic effects (immune response in all participants revealed by antibody titration), while mild effects were observed after the two required doses. This research opened the way to Phase II/III trials, followed by the approval of both drugs in different countries. The vaccines are now being deployed worldwide.