Streamlining Genetic Safety Analysis for Ex Vivo Genome Edited Cell Therapies
June 2, 2020
- June 2, 2020
University of California, San Francisco (UCSF) – Stanford University CERSI
Tuesday, June 2, 2020
Matthew Porteus, MD, PhD
Professor, Department of Pediatrics, Institute of Stem Cell Biology and Regenerative Medicine and Maternal-Child Health Research Institute
About the Presentation
Genome editing is an emerging and exciting new technology that is being discussed as a potential method to treat a range of diseases that have large unmet medical needs. The goal of ex vivo genome editing is to modify the sequence of a cell that will be given to a patient with single nucleotide precision. However, in the process of creating such precise changes, mutations can be induced at off-target sites. There have been numerous methods described in published literature that propose how to identify lists of potential off-target sites including bioinformatic methods, cell-based methods, and in vitro methods, but there has been no systematic and unbiased examination of which method generates a list of potential off-target sites that is both complete and concise in terms of which of these potential sites are actual sites of insertions/deletions using clinically relevant cell types. This lecture discussed the process of generating data to assess which methods of identifying potential off-target sites using the CRISPR/Cas9 system identify bona fide off-target sites using clinically relevant ex vivo genome editing reagents. These data helped the field of ex vivo genome editing better understand which of the methods provided the best way to generate a list of potential off-target sites that should be experimentally assessed during the clinical development of an ex vivo genome edited cell-based product and potentially streamline the toxicology evaluation for INDs.
About the Presenter
Matthew Porteus MD, PhD is a Professor in the Department of Pediatrics and Institute of Stem Cell Biology and Regenerative Medicine and Maternal-Child Health Research Institute at Stanford. His primary research focus is on developing genome editing as an approach to cure disease, particularly those of the blood (such as sickle cell disease) but also of other organ systems as well. He received his undergraduate degree at Harvard in History and Science where his honors thesis studied the recombinant DNA controversy of the 1970s. He then completed his MD and PhD training at Stanford, clinical training in Pediatric Hematology/Oncology at Boston Children’s Hospital, and post-doctoral research training with Noble Laureate David Baltimore at CalTech. He works as an attending physician on the Pediatric Hematopoietic Stem Cell Transplant service at Lucile Packard Children’s Hospital where he cares for children under going bone marrow transplantation for both malignant and non-malignant diseases. His goal is to combine his research and clinical interests to develop innovative curative therapies. He served on the 2017 National Academy Study Committee of Human Genome Editing and currently serves on the Scientific Advisory Board for WADA on Cell and Gene Doping and the NIH NexTRAC advisory committee evaluating the emergence of new technologies.
FOR QUESTIONS and REASONABLE ACCOMMODATIONS:
Please contact Rebekah Zinn at Rebekah.Zinn@fda.hhs.gov.