Search: onr:"swepub:oai:DiVA.org:su-196280" >
Profiling of Extrac...
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Sork, HelenaKarolinska Institutet
(author)
Profiling of Extracellular Small RNAs Highlights a Strong Bias towards Non-Vesicular Secretion
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-06-18
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MDPI AG,2021
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:su-196280
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-196280URI
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https://doi.org/10.3390/cells10061543DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:146991633URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The extracellular environment consists of a plethora of molecules, including extracellular miRNA that can be secreted in association with extracellular vesicles (EVs) or soluble protein complexes (non-EVs). Yet, interest in therapeutic short RNA carriers lies mainly in EVs, the vehicles conveying the great majority of the biological activity. Here, by overexpressing miRNA and shRNA sequences in parent cells and using size exclusion liquid chromatography (SEC) to separate the secretome into EV and non-EV fractions, we saw that >98% of overexpressed miRNA was secreted within the non-EV fraction. Furthermore, small RNA sequencing studies of native miRNA transcripts revealed that although the abundance of miRNAs in EVs, non-EVs and parent cells correlated well (R-2 = 0.69-0.87), quantitatively an outstanding 96.2-99.9% of total miRNA was secreted in the non-EV fraction. Nevertheless, though EVs contained only a fraction of secreted miRNAs, these molecules were stable at 37 degrees C in a serum-containing environment, indicating that if sufficient miRNA loading is achieved, EVs can remain delivery-competent for a prolonged period of time. This study suggests that the passive endogenous EV loading strategy might be a relatively wasteful way of loading miRNA to EVs, and active miRNA loading approaches are needed for developing advanced EV miRNA therapies in the future.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Conceicao, Mariana
(author)
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Corso, GiuliaKarolinska Institutet
(author)
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Nordin, JoelKarolinska Institutet
(author)
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Lee, Yi Xin Fiona
(author)
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Krjutskov, Kaarel
(author)
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Orzechowski Westholm, JakubStockholms universitet,Science for Life Laboratory (SciLifeLab),Institutionen för biokemi och biofysik(Swepub:su)jaor0050
(author)
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Vader, Pieter
(author)
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Pauwels, Marie
(author)
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Vandenbroucke, Roosmarijn E.
(author)
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Wood, Matthew J. A.
(author)
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EL Andaloussi, SamirKarolinska Institutet
(author)
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Mager, Imre
(author)
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Karolinska InstitutetScience for Life Laboratory (SciLifeLab)
(creator_code:org_t)
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In:Cells: MDPI AG10:62073-4409
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Sork, Helena
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Conceicao, Maria ...
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Corso, Giulia
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Nordin, Joel
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Lee, Yi Xin Fion ...
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Krjutskov, Kaare ...
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Orzechowski West ...
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Vader, Pieter
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Pauwels, Marie
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Vandenbroucke, R ...
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Wood, Matthew J. ...
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EL Andaloussi, S ...
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Mager, Imre
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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Cells
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Stockholm University
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Karolinska Institutet