SC1: Gene Editing For Targeted Therapies

MONDAY, OCTOBER 19 | 10:00 – 1:00 PM

ABOUT THIS COURSE:

While the challenges and risks associated with oligonucleotide therapies still remain, there is a new and better understanding of how DNA and RNA can be effectively manipulated and delivered. With the rise of gene editing tools and enhanced knowledge of targeted delivery, these therapeutic modalities are once again being embraced with renewed hope and enthusiasm. This course helps you understand how gene editing, base editing and RNA editing – particularly the one enabled by the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system – works, and how it can be used to help develop targeted therapies.

COURSE AGENDA:

10:00 Welcome Remarks and Speaker Introductions

10:10 Gene Editing and Blastocyst Complementation to Grow Human Organs in Pigs

Clifford Steer, MD, Professor of Medicine and Genetics, Cell Biology, and Development, University of Minnesota Medical School

• Describe the role of gene editing and blastocyst complementation in generating chimeric livers in pigs
• Discuss the potential challenges in bringing such a technology to commercialization and the bedside
• Predict the future for organ transplantation based on current and developing technologies
  

10:40 Gene-edited Cell-based Therapies

Khalid Shah, MS, PhD, Director, Center for Stem Cell Therapies and Imaging, Harvard Medical School; Vice Chair of Research, Brigham and Women’s Hospital

• Sources of therapeutic cells (Stem cells, T cells, NK cells and Cancer cells)
• Novel engineered viral vectors and their engineering capabilities
• Role of CRISPR gene editing in creating therapeutic cells
• Applications of gene edited cells in pre-clinical models
• Clinical translation and safety aspects of engineered cell therapies

11:10 Coffee Break

11:30 Next Generation of Editors: Base Editor and Prime Editor

Branden Moriarity, PhD, Assistant Professor, Department of Pediatrics, University of Minnesota Medical School

• Introduction to base editing and prime editing
• Applications in cell therapy

12:00 Harnessing Novel CRISPR Systems for Transcriptome Engineering 

Jonathan Gootenberg, PhD, McGovern Fellow, McGovern Institute for Brain Research, MIT

Omar Abudayyeh, PhD, McGovern Fellow, McGovern Institute for Brain Research, MIT

• Many novel DNA and RNA targeting CRISPR systems can be found from bacterial genome mining
• Cas13 is a programmable RNA targeting system that can be used for RNA base editing
• REPAIR and RESCUE Cas13 RNA editors are capable of correcting disease-relevant mutations in RNA

12:45 Q&A with attendees

1:00 End of Course

INSTRUCTOR BIOGRAPHIES:

Clifford Steer, MD, Professor of Medicine and Genetics, Cell Biology, and Development, University of Minnesota Medical School

Clifford J. Steer is a Professor of Medicine and Genetics, Cell Biology, and Development at the University of Minnesota, Minneapolis, MN. He has been active in the field of liver research for more than four decades. In that capacity, he has been a long-standing member of several National Institutes of Health Study Sections. He has been co-editor of a major scientific journal in liver diseases and presently serves on the editorial boards of three journals. Steer’s areas of research over the past decade have included gene therapy, liver regeneration, neurodegeneration and microRNA regulation of gene function. He has published over 300 articles; and has organized and chaired many national and international scientific conferences. In recognition of his work, he was made an inaugural Fellow of the American Association for the Study of Liver Diseases in 2014.

Khalid Shah, MS, PhD, Director, Center for Stem Cell Therapies and Imaging, Harvard Medical School; Vice Chair of Research, Brigham and Women’s Hospital

Khalid Shah, MS, PhD is the Director of the Center for Stem Cell Therapeutics and Imaging and the Center of Excellence in Biomedicine at Brigham and Women’s Hospital (BWH). He is also the Vice Chair of Research for the Department of Neurosurgery at BWH and a Principal Faculty at Harvard Stem Cell Institute in Boston. Dr. Shah and his team have pioneered major developments in the cell therapy field, successfully developing experimental models to understand basic cancer biology and therapeutic cells for cancer. Recently, Dr. Shah’s laboratory has reverse engineered cancer cells using CRISPR/Cas9 technology and utilized them as therapeutics to treat cancer. He has founded 2 biotech companies, AMASA Therapeutics and ALIM Therapeutics, whose main objective is the clinical translation of therapeutic stem cells in cancer patients.

Branden Moriarity, PhD, Assistant Professor, Department of Pediatrics, University of Minnesota Medical School

Dr. Moriarity is currently an Assistant Professor in the Department of Pediatrics, Division of Hematology/Oncology. He graduated from Saint Olaf College in 2007 with a BA in Biology, Chemistry, and Biomolecular sciences. He received his Ph.D. in Molecular, Cellular, Developmental Biology & Genetics at the University of Minnesota in 2012. From 2012-2014 he was post-doctoral fellow in David Largaespda’s lab where he worked on identifying the genetics of pediatric sarcomas. Dr. Moriarity joined the Department of Pediatrics Faculty as an Assistant Professor in 2014. Dr. Moriarity runs a basic/translational research laboratory working to develop novel cellular therapeutics for gene therapy and cancer immunotherapy with the goal of translating new therapeutics to the clinic. To accomplish these goals the Moriarity lab uses cutting edge genome engineering technologies including CRISPR/Cas9, base editor technology, transposons, and rAAV. These tools allow for high frequency gene knockout, gene knock-in, induction of targeted sequence changes, and activation and/or repression of endogenous gene expression. Target cells for engineering include T cells, B cells, NK cells, Monocytes, and hematopoietic stem cells. In addition to developing cellular based therapeutics, the Moriarity lab also performs preclinical drug testing for pediatric cancers, such as osteosarcoma, in order to launch new clinical trials using antibody therapies rather than toxic chemotherapy.

Jonathan Gootenberg, PhD, McGovern Fellow, McGovern Institute for Brain Research, MIT

Jonathan Gootenberg draws from fundamental microbiology to engineer new molecular tools. These tools, including the popular genome editing system CRISPR, allow for unprecedented manipulation and profiling of cellular states in the body, and have multiple applications in basic science, diagnostics, and therapeutics. Dr. Gootenberg uses gene editing, gene delivery, and cellular profiling methods to understand the changes that occur in the brain and other organs during aging, with the goal of generating new therapies for degenerative disease. Dr. Gootenberg earned his bachelor’s degree in mathematics and biological engineering at MIT and received his PhD in Systems Biology from Harvard University, during which he conducted research with Aviv Regev and Feng Zhang at the McGovern Institute and Broad Institute of MIT and Harvard. During his PhD, Gootenberg focused on the development of molecular technologies for treating and sensing disease states, crossing disciplines by utilizing novel computational techniques, microbiology, biochemistry, and molecular biology to uncover new CRISPR tools, including Cas12 and Cas13. He and his co-authors developed Cas13 into a toolbox with uses in fundamental research, therapeutics, and diagnostics. These applications include RNA knockdown, imaging, the base editing platform REPAIR, and the sensitive, specific, and portable diagnostic platform SHERLOCK. He is one of the first members of the McGovern Institute Fellows program, which supports the transition to independent research for exceptional recent PhD graduates.

Omar Abudayyeh, PhD, McGovern Fellow, McGovern Institute for Brain Research, MIT

Omar Abudayyeh, Ph.D., is a McGovern Institute Fellow at the Massachusetts Institute of Technology where he leads a lab on exploring microbial diversity for new biotechnological tools related to genome editing and gene delivery. He previously was at Harvard Medical School and the Harvard-MIT Health Sciences and Technology program as a graduate student. He completed his doctoral work in Feng Zhang’s lab at the Broad Institute of MIT and Harvard, where his research centered on novel CRISPR enzymes for applications in genome editing, therapeutics, and diagnostics. Dr. Abudayyeh’s work focused on uncovering novel CRISPR enzymes beyond Cas9 for biotechnological applications. He co-led the discovery and characterization of multiple landmark pieces of work, including the characterization of Cpf1 for novel genome editing applications and the first single-protein RNA-guided RNA-targeting enzyme C2c2/Cas13. His follow-up work on C2c2/Cas13 biology led to the development of SHERLOCK technology, and a new set of tools for precise editing of transcripts and visualizing them in mammalian cells with potential for RNA therapeutics. In recognition of his technology developments, Dr. Abudayyeh was recognized as 2018 Forbes 30 under 30 in Science and Health Care and Business Insider 30 under 30. Dr. Abudayyeh graduated from MIT in 2012 with a B.S. in mechanical engineering and biological engineering, where he was a Henry Ford II Scholar and a Barry M. Goldwater Scholar.