Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles
dc.contributor.author | Biscans, Annabelle | |
dc.contributor.author | Haraszti, Reka A | |
dc.contributor.author | Echeverria, Dimas | |
dc.contributor.author | Miller, Rachael | |
dc.contributor.author | Didiot, Marie C. | |
dc.contributor.author | Nikan, Mehran | |
dc.contributor.author | Roux, Loic | |
dc.contributor.author | Aronin, Neil | |
dc.contributor.author | Khvorova, Anastasia | |
dc.date | 2022-08-11T08:10:52.000 | |
dc.date.accessioned | 2022-08-23T17:22:57Z | |
dc.date.available | 2022-08-23T17:22:57Z | |
dc.date.issued | 2018-06-06 | |
dc.date.submitted | 2019-09-18 | |
dc.identifier.citation | <p>Mol Ther. 2018 Jun 6;26(6):1520-1528. doi: 10.1016/j.ymthe.2018.03.019. Epub 2018 Apr 4. <a href="https://doi.org/10.1016/j.ymthe.2018.03.019">Link to article on publisher's site</a></p> | |
dc.identifier.issn | 1525-0016 (Linking) | |
dc.identifier.doi | 10.1016/j.ymthe.2018.03.019 | |
dc.identifier.pmid | 29699940 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/48854 | |
dc.description.abstract | Small extracellular vesicles (sEVs) show promise as natural nano-devices for delivery of therapeutic RNA, but efficient loading of therapeutic RNA remains a challenge. We have recently shown that the attachment of cholesterol to small interfering RNAs (siRNAs) enables efficient and productive loading into sEVs. Here, we systematically explore the ability of lipid conjugates-fatty acids, sterols, and vitamins-to load siRNAs into sEVs and support gene silencing in primary neurons. Hydrophobicity of the conjugated siRNAs defined loading efficiency and the silencing activity of siRNA-sEVs complexes. Vitamin-E-conjugated siRNA supported the best loading into sEVs and productive RNA delivery to neurons. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=29699940&dopt=Abstract">Link to Article in PubMed</a></p> | |
dc.relation.url | https://doi.org/10.1016/j.ymthe.2018.03.019 | |
dc.rights | Copyright © 2018 The American Society of Gene and Cell Therapy. Under a Creative Commons license, https://creativecommons.org/licenses/by-nc-nd/4.0/, per article landing page at https://doi.org/10.1016/j.ymthe.2018.03.019. | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Biochemistry, Biophysics, and Structural Biology | |
dc.subject | Cell and Developmental Biology | |
dc.subject | Genetics and Genomics | |
dc.subject | Therapeutics | |
dc.title | Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles | |
dc.type | Journal Article | |
dc.source.journaltitle | Molecular therapy : the journal of the American Society of Gene Therapy | |
dc.source.volume | 26 | |
dc.source.issue | 6 | |
dc.identifier.legacyfulltext | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1061&context=rti_pubs&unstamped=1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/rti_pubs/62 | |
dc.identifier.contextkey | 15358663 | |
refterms.dateFOA | 2022-08-23T17:22:57Z | |
html.description.abstract | <p>Small extracellular vesicles (sEVs) show promise as natural nano-devices for delivery of therapeutic RNA, but efficient loading of therapeutic RNA remains a challenge. We have recently shown that the attachment of cholesterol to small interfering RNAs (siRNAs) enables efficient and productive loading into sEVs. Here, we systematically explore the ability of lipid conjugates-fatty acids, sterols, and vitamins-to load siRNAs into sEVs and support gene silencing in primary neurons. Hydrophobicity of the conjugated siRNAs defined loading efficiency and the silencing activity of siRNA-sEVs complexes. Vitamin-E-conjugated siRNA supported the best loading into sEVs and productive RNA delivery to neurons.</p> | |
dc.identifier.submissionpath | rti_pubs/62 | |
dc.contributor.department | Graduate School of Biomedical Sciences, Translational Science Program | |
dc.contributor.department | Department of Medicine | |
dc.contributor.department | Program in Molecular Medicine | |
dc.contributor.department | RNA Therapeutics Institute | |
dc.source.pages | 1520-1528 |