Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal DNA is both methylated and fully recapitulates the methylation patterns observed in the cells of origin. We also propose a potential mechanism for DNA packaging into exosomes by disruption of the nuclear membrane. Finally, we investigated the ability of exosomes to induce paracrine DNA damage responses (DDR) in treatment-naïve cells. We explore the specificity of exosome-induced DDR to exosomes released by damaged cancer cells, and provide a potential molecular mechanism of action via the shuttling of activated DDR pathway proteins.
","abstract_html":"<p>Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal DNA is both methylated and fully recapitulates the methylation patterns observed in the cells of origin. We also propose a potential mechanism for DNA packaging into exosomes by disruption of the nuclear membrane. Finally, we investigated the ability of exosomes to induce paracrine DNA damage responses (DDR) in treatment-naïve cells. We explore the specificity of exosome-induced DDR to exosomes released by damaged cancer cells, and provide a potential molecular mechanism of action via the shuttling of activated DDR pathway proteins.</p>","abstract_has_math":false,"creators":["Tavormina, Jena","0000-0003-4869-7866
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"]},{"key":"dc:title","label":"Title","values":["Identification and Molecular Analysis of Dna In Exosomes"]}]}],"canonical_facts":{"dc:contributor":["Raghu Kalluri MD., PhD.","Menashe Bar-Eli, PhD.","Joya Chandra, PhD."],"dc:creator":["Tavormina, Jena","0000-0003-4869-7866
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"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/981"],"dc:subject":["Exosomes","DNA","Methylation","DNA Damage Response","Liquid Biopsy","Biological Phenomena, Cell Phenomena, and Immunity","Diagnosis","Medical Cell Biology","Medical Genetics","Medical Molecular Biology","Medicine and Health Sciences","Nanomedicine","Oncology","Therapeutics"],"dc:title":["Identification and Molecular Analysis of Dna In Exosomes"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:49:16Z"}