Event
BIOE Seminar Series: Angela Pannier (University of Nebraska)
Friday, January 29, 2021
9:00 a.m.-10:00 a.m.
Virtual
Steven Jay
smjay@umd.edu
The Spring 2021 seminars will be held virtually on Fridays from 9:00 a.m. – 9:50 a.m., unless otherwise noted. All BIOE faculty, students, staff, postdocs, and affiliates as well as additional subscribers to our weekly seminars emails will receive Zoom event information the week of each seminar.
If you do not yet receive our weekly seminars email and would like to subscribe to the listserv, or if you would like to attend this particular seminar, please email Emily Rosenthal.
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Maxcy Professor of Agriculture and Natural Resources
Professor of Biomedical Engineering
Using Cell Priming and Modeling to Understand and Enhance Nonviral Gene Delivery to Stem Cells for CRISPR and Exosome Applications
Gene delivery can revolutionize treatment and prevention of diseases but requires a carrier to transport exogenous genes into cells to produce an encoded protein. Nonviral gene delivery carriers are an attractive alternative to viral systems because of low toxicity and immunogenicity, lack of pathogenicity, inexpensive synthesis, and easy modification. However, nonviral delivery systems suffer from a lack of efficiency compared to their viral counterparts, especially in adult-derived stem cells. Previous investigations into enhancing transfection of nonviral systems have focused on physicochemical modification of carriers to overcome barriers that limit efficiency. However, design of DNA delivery systems is limited because specific molecules and pathways that facilitate transfection remain unknown. In our work, we have used microarray analysis of transfected cells to identify molecular mediators of nonviral gene delivery as potential endogenous targets for rational design of carriers, and are developing the idea of “cell priming” of those targets as a simple and clinically translatable strategy for improved gene transfer. In cell priming, a pharmacologic agent is delivered to cells prior to delivery of DNA to modifycellular responsiveness to gene transfer. In addition to increasing understanding of transfection, identification of cell priming strategies that dramatically enhance transfection efficiencies promises to lead to simple new gene delivery protocols, applicable to many carrier and cell types. To increase our library of priming candidates, we have performed large-scale screens of clinically approved drugs to identify new priming targets and agents and have identified glucocorticoids as a class of cell priming adjuvants that significantly enhance transfection in human mesenchymal stem cells (hMSCs). We have also developed a new mathematical model to describe the process of gene delivery based on telecommunications theory, where delivery of DNA to the cellnucleus is analogous to delivery of a packet of information (DNA) to a destination computer (nucleus) within a random, packet-switched computer network(cell). Outputs from this new model show agreement with experimental data and we are using the model to make a priori predictions, to identify improvements to gene delivery systems and guide designs of therapeutically relevant carriers, to improve DNA delivery to hMSCs for applications ranging from exosome production to cell therapies enabled by gene editing.
