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Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles.
Biscans, Annabelle; Haraszti, Reka A; Echeverria, Dimas; Miller, Rachael; Didiot, Marie-Cecile; Nikan, Mehran; Roux, Loic; Aronin, Neil; Khvorova, Anastasia.
Affiliation
  • Biscans A; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Haraszti RA; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Echeverria D; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Miller R; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Didiot MC; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Nikan M; Ionis Pharmaceutical, Carlsbad, CA 92010, USA.
  • Roux L; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Aronin N; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: neil.aronin@umassmed.edu.
  • Khvorova A; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: anastasia.khvorova@umassmed.edu.
Mol Ther ; 26(6): 1520-1528, 2018 06 06.
Article in En | MEDLINE | ID: mdl-29699940
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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Full text: 1 Database: MEDLINE Main subject: RNA, Small Interfering / Extracellular Vesicles / Lipids Type of study: Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Year: 2018 Type: Article
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Full text: 1 Database: MEDLINE Main subject: RNA, Small Interfering / Extracellular Vesicles / Lipids Type of study: Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Year: 2018 Type: Article