{"634264":{"#nid":"634264","#data":{"type":"event","title":"PhD Defense by Kalina Paunovska ","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EKalina Paunovska \u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EBME PhD Thesis Defense\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EDate:\u003C\/strong\u003E\u0026nbsp;May 6th, 2020\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ETime:\u003C\/strong\u003E\u0026nbsp;1:00 PM\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EBluejeans:\u0026nbsp;\u003C\/strong\u003E\u003Ca href=\u0022https:\/\/bluejeans.com\/385189433\u0022 target=\u0022_blank\u0022\u003Ehttps:\/\/bluejeans.com\/385189433\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EJames E. Dahlman, Ph.D. (Advisor)\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAndres Garcia, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EPhilip J. Santangelo, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EEdward Botchwey, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EJulie Champion, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDepartment of Chemical and Biomolecular Engineering, Georgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ETitle:\u003C\/strong\u003E\u0026nbsp;An investigation of parameters that influence non-hepatocyte RNA delivery\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EAbstract:\u0026nbsp;\u003C\/strong\u003ELipid nanoparticle (LNP)-mediated nucleic acid delivery can regulate the expression of any gene, making it a promising way to treat disease. However, clinically relevant delivery of RNA therapeutics to non-hepatocytes\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E\u0026nbsp;remains challenging.\u0026nbsp;Most LNPs are created by mixing an ionizable lipid with PEG, a phospholipid, and cholesterol, allowing the possibility for thousands of chemically distinct LNPs. These nanoparticles are typically screened\u0026nbsp;\u003Cem\u003Ein vitro\u003C\/em\u003E\u0026nbsp;in easily expandable cell lines, yet these cell culture conditions are not representative of\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E\u0026nbsp;tissue microenvironments. LNPs that deliver their payload (e.g. DNA, RNA) successfully\u0026nbsp;\u003Cem\u003Ein vitro\u003C\/em\u003E\u0026nbsp;are then validated\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E. However, because LNPs that tend to work\u0026nbsp;\u003Cem\u003Ein vitro\u003C\/em\u003E\u0026nbsp;do not necessarily work\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E, this often leads to a small number of viable candidates. The objective of this thesis is to use high-throughput DNA barcoding to ask fundamental questions about\u003Cem\u003E\u0026nbsp;in vivo\u0026nbsp;\u003C\/em\u003Edrug delivery. In particular, this work presents four significant contributions to the field of nucleic acid delivery. First, this work explores\u0026nbsp;\u003Cem\u003Ein vitro\u0026nbsp;\u003C\/em\u003Eand\u0026nbsp;\u003Cem\u003Ein vivo\u0026nbsp;\u003C\/em\u003ELNP delivery in many cell types (e.g. endothelial, macrophage) from many tissues (e.g. heart, lung, bone marrow) and reveals that\u0026nbsp;\u003Cem\u003Ein vitro\u003C\/em\u003E\u0026nbsp;LNP delivery is not predictive of\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E\u0026nbsp;delivery. Second, cholesterol structure \u0026ndash; a previously unperturbed LNP component \u0026ndash; is found to impact LNP delivery\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E. Cholesterol variants are naturally trafficked in lipoproteins (e.g. LDL, VLDL) suggesting that LNP targeting can be tuned by using naturally- or synthetically-derived cholesterol variants. Third, LNPs that deliver RNA to non-hepatocytes more efficiently than to hepatocytes are identified. Fourth, manipulating cell metabolism through exogenous administration of a small molecule is found to impact LNP-delivered mRNA translation\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E. Finally, the potential for related works and new directions worthy of pursuit within the field nucleic acid drug delivery are discussed. Taken together, this work enables understanding and optimization of the factors that influence non-hepatocyte RNA delivery\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E.\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"An investigation of parameters that influence non-hepatocyte RNA delivery in vivo"}],"uid":"27707","created_gmt":"2020-04-10 15:26:03","changed_gmt":"2020-04-10 15:26:03","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2020-05-06T14:00:00-04:00","event_time_end":"2020-05-06T16:00:00-04:00","event_time_end_last":"2020-05-06T16:00:00-04:00","gmt_time_start":"2020-05-06 18:00:00","gmt_time_end":"2020-05-06 20:00:00","gmt_time_end_last":"2020-05-06 20:00:00","rrule":null,"timezone":"America\/New_York"},"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":"78761","name":"Faculty\/Staff"},{"id":"78771","name":"Public"},{"id":"174045","name":"Graduate students"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}