UMMS Affiliation

RNA Therapeutics Institute; Department of Medicine; Mass Spectrometry Facility; Department of Biochemistry and Molecular Pharmacology; MassBiologics; Program in Molecular Medicine; Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program

Publication Date

2019-05-27

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry | Cell Biology | Cells | Enzymes and Coenzymes | Lipids | Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides | Therapeutics

Abstract

Exosomes can serve as delivery vehicles for advanced therapeutics. The components necessary and sufficient to support exosomal delivery have not been established. Here we connect biochemical composition and activity of exosomes to optimize exosome-mediated delivery of small interfering RNAs (siRNAs). This information is used to create effective artificial exosomes. We show that serum-deprived mesenchymal stem cells produce exosomes up to 22-fold more effective at delivering siRNAs to neurons than exosomes derived from control cells. Proteinase treatment of exosomes stops siRNA transfer, indicating that surface proteins on exosomes are involved in trafficking. Proteomic and lipidomic analyses show that exosomes derived in serum-deprived conditions are enriched in six protein pathways and one lipid class, dilysocardiolipin. Inspired by these findings, we engineer an "artificial exosome," in which the incorporation of one lipid (dilysocardiolipin) and three proteins (Rab7, Desmoplakin, and AHSG) into conventional neutral liposomes produces vesicles that mimic cargo delivering activity of natural exosomes.

Keywords

Biochemistry, Biological Sciences, Lipidomics, Molecular Biology, Proteomics

Rights and Permissions

Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of Published Version

10.1016/j.isci.2019.05.029

Source

iScience. 2019 May 27;16:230-241. doi: 10.1016/j.isci.2019.05.029. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

iScience

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

31195240

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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