RNA Therapeutics Institute; Program in Molecular Medicine; Department of Medicine; Graduate School of Biomedical Sciences, Translational Science Program
Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Genetics and Genomics | Therapeutics
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.
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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.
DOI of Published Version
Mol Ther. 2018 Jun 6;26(6):1520-1528. doi: 10.1016/j.ymthe.2018.03.019. Epub 2018 Apr 4. Link to article on publisher's site
Molecular therapy : the journal of the American Society of Gene Therapy
Biscans, Annabelle; Haraszti, Reka A.; Echeverria, Dimas; Miller, Rachael; Didiot, Marie C.; Nikan, Mehran; Roux, Loic; Aronin, Neil; and Khvorova, Anastasia, "Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles" (2018). RNA Therapeutics Institute Publications. 62.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.