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Grossen, Philip; Portmann, Michaela; Koller, Erich; Duschmalé, Martina; Minz, Tanja; Sewing, Sabine; Pandya, Nikhil Janak; van Geijtenbeek, Sabine Kux; Ducret, Axel; Kusznir, Eric-André; Huber, Sylwia; Berrera, Marco; Lauer, Matthias E.; Ringler, Philippe; Nordbo, Bettina; Jensen, Marianne Lerbech; Sladojevich, Filippo; Jagasia, Ravi; Alex, Rainer; Gamboni, Remo; Keller, Michael
European journal of pharmaceutics and biopharmaceutics, January 2021, 2021-Jan, 2021-01-00, 20210101, Letnik: 158Journal Article
Display omitted The natural capacity of extracellular vesicles (EVs) to transport their payload to recipient cells has raised big interest to repurpose EVs as delivery vehicles for xenobiotics. In the present study, bovine milk-derived EVs (BMEVs) were investigated for their potential to shuttle locked nucleic acid-modified antisense oligonucleotides (LNA ASOs) into the systemic circulation after oral administration. To this end, a broad array of analytical methods including proteomics and lipidomics were used to thoroughly characterize BMEVs. We found that additional purification by density gradients efficiently reduced levels of non-EV associated proteins. The potential of BMEVs to functionally transfer LNA ASOs was tested using advanced in vitro systems (i.e. hPSC-derived neurons and primary human cells). A slight increase in cellular LNA ASO internalization and target gene reduction was observed when LNA ASOs were delivered using BMEVs. When dosed orally in mice, only a small fraction (about 1% of total administered dose) of LNA ASOs was recovered in the peripheral tissues liver and kidney, however, no significant reduction in target gene expression (i.e. functional knockdown) was observed.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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