La Trobe

File(s) under permanent embargo

Proteomic and Post‐Translational Modification Profiling of Exosome‐Mimetic Nanovesicles Compared to Exosomes

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Issues associated with upscaling exosome production for therapeutic use may be overcome through utilizing artificial exosomes. Cell-derived mimetic nanovesicles (M-NVs) are a potentially promising alternative to exosomes for clinical applicability, demonstrating higher yield without incumbent production and isolation issues. Although several studies have shown that M-NVs have similar morphology, size and therapeutic potential compared to exosomes, comprehensive characterization and to what extent M-NVs components mimic exosomes remain elusive. M-NVs were generated through the extrusion of cells and proteomic profiling demonstrated an enrichment of proteins associated with membrane and cytosolic components. The proteomic data herein reveal a subset of proteins that are highly abundant in M-NVs in comparison to exosomes. M-NVs contain proteins that largely represent the parental cell proteome, whereas the profile of exosomal proteins highlight their endosomally derived origin. This advantage of M-NVs alleviates the necessity of endosomal sorting of endogenous therapeutic proteins or RNA into exosomes. This study also highlights differences in protein post-translational modifications among M-NVs, as distinct from exosomes. Overall this study provides key insights into defining the proteome composition of M-NVs as a distinct from exosomes, and the potential advantage of M-NVs as an alternative nanocarrier when spontaneous endosomal sorting of therapeutics are limited.

Funding

A.N.K. and K.K. contributed equally to this work. This work was supported by grants from the Australian Research Council (DP170102312 to A.F.H). A.N.K. is supported by a La Trobe University Postgraduate Scholarship. The authors acknowledge the La Trobe University-Comprehensive Proteomics Platform for providing infrastructure. The Lundbeck Foundation grant (R247-2017-239) and The Danish National Mass Spectrometry Platform for Functional Proteomics (PRO-MS; grant no. 5072-00007B), the Obel Family Foundation, and the Svend Andersen Foundation are acknowledged for parts of this study.

History

Publication Date

01/04/2019

Journal

Proteomics

Volume

19

Issue

8

Article Number

1800161

Pagination

20p. (p. 1800161-1800161)

Publisher

Wiley

ISSN

1615-9853

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.