{"675533":{"#nid":"675533","#data":{"type":"event","title":"PhD Defense by Steven Narum","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003ESteven Narum\u003C\/strong\u003E\u003Cbr\u003E\u003Cstrong\u003EBME PhD Defense Presentation\u003C\/strong\u003E\u003Cbr\u003E\u003Cbr\u003E\u003Cstrong\u003EDate: 2024-07-30\u003C\/strong\u003E\u003Cbr\u003E\u003Cstrong\u003ETime: 1:00 PM to 3:00 PM\u003C\/strong\u003E\u003Cbr\u003E\u003Cstrong\u003ELocation \/ Meeting Link: Atwood 316 \u003C\/strong\u003E\u003Ca href=\u0022https:\/\/emory.zoom.us\/j\/91676986251\u0022\u003E\u003Cstrong\u003Ehttps:\/\/emory.zoom.us\/j\/91676986251\u003C\/strong\u003E\u003C\/a\u003E\u003Cbr\u003E\u003Cbr\u003E\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u003Cbr\u003E\u003Cstrong\u003EKhalid Salaita, Ph.D.; Hanjoong Jo, Ph.D.; Yonggang Ke, Ph.D.; Julie Champion, Ph.D.; Krishnendu Roy, Ph.D.\u003C\/strong\u003E\u003Cbr\u003E\u003Cbr\u003E\u003Cbr\u003E\u003Cstrong\u003ETitle: Rational Design of a Modular Endosomal Escape Platform to Improve Cytosolic Delivery of Nucleic Acids\u003C\/strong\u003E\u003Cbr\u003E\u003Cbr\u003E\u003Cstrong\u003EAbstract:\u003C\/strong\u003E\u003Cbr\u003E\u003Cstrong\u003EEndocytosis has long served as a major bottleneck toward nucleic acid delivery as this class of drugs remain trapped within endosomes. Current research trends to overcome endosomal entrapment provide varied success; however, active delivery agents such as endosomal escape peptides (EEP) have emerged as a prominent strategy to improve cytosolic delivery. Yet, EEPs have poor selectivity between endosomal membranes and cellular membranes, leading to toxicity in clinical trials. In this dissertation, I characterize and optimize a pH triggerable trojan horse gene therapeutic that provides a smart ASO release with endosomal acidification and selective membrane disruptive activity. We discovered that an i-Motif duplex undergoes a pH-mediated structure-switch to trigger release of an antisense drug. I further explore cellular cues and learn that nucleases are important in mediating this delivery. Additionally, I explore the application of fluorescence lifetime imaging microscopy (FLIM) to study and visualize the subcellular localization and degradation of spherical nucleic acids (SNAs). I discovered that PS-modified backbones, even in a SNA construct, vastly improve the stability and resistance to nucleases; however, dithiol modifications do not benefit stability nearly to the same extent despite increased thiol-displacement resistance. We show that FLIM measurements are sensitive to the initial stages of SNA dissociation and is a powerful tool to characterize intracellular trafficking. Lastly, I develop the foundation for a biocompatible nanoparticle platform that is clinically viable and therapeutically active. Overall, by addressing current limitations in drug delivery, this work will advance nanomedicine as a whole and provide new techniques for developing smart nanotechnologies and overcoming intracellular barriers.\u003C\/strong\u003E\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003ERational Design of a Modular Endosomal Escape Platform to Improve Cytosolic Delivery of Nucleic Acids\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Rational Design of a Modular Endosomal Escape Platform to Improve Cytosolic Delivery of Nucleic Acids"}],"uid":"27707","created_gmt":"2024-07-19 15:28:57","changed_gmt":"2024-07-19 15:29:23","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2024-07-30T13:30:00-04:00","event_time_end":"2024-07-30T15:30:00-04:00","event_time_end_last":"2024-07-30T15:30:00-04:00","gmt_time_start":"2024-07-30 17:30:00","gmt_time_end":"2024-07-30 19:30:00","gmt_time_end_last":"2024-07-30 19:30:00","rrule":null,"timezone":"America\/New_York"},"location":" Atwood 316 ","extras":[],"groups":[{"id":"221981","name":"Graduate Studies"}],"categories":[],"keywords":[{"id":"100811","name":"Phd Defense"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[{"id":"78771","name":"Public"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}