TARGETED DRUG DELIVERY USING EXTRACELLULAR VESICLES
- 技術優勢
- Increased target affinity and specificity compared to peptidesIncreased cellular uptake of EVs (in vivo or in vitro) Directed EVs to particular uptake pathways via targeted receptors (in vivo or in vitro) Biological incorporation of the targeting moiety occurs during EV biogenesis rather than through chemical methods Addition of a targeting moiety to the EV surface can occur post EV production/purification
- 詳細技術說明
- Stable and non-toxic extracellular vesicles for targeted drug delivery. #therapeutics #drugdelivery
- *Abstract
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BACKGROUND
Extracellular vesicles (EVs) are nanoscale particles secreted by nearly all cell types that encapsulate cellular contents such as protein and nucleic acids. They are important mediators of intercellular communication because of their ability to transfer biomolecules between cells. While these properties make them an attractive platform for delivering therapeutics, targeting EVs to specific cell types remains challenging. To date, targeting is primarily achieved by displaying peptides on the EV surface to promote uptake by specific cells, but results have been variable and effects modest. Alternative approaches require adding targeting domains post-harvest of EVs, which complicates bioprocessing and may limit functionality.
ABSTRACT
Northwestern inventors have developed a novel method to help increase the affinity of extracellular vesicles (EVs) for a targeted recipient cell using by displaying domain-based targeting proteins on the EV surface. This approach method increases EV uptake by the recipient cells, enhances functional delivery of cargo by EVs, and reduces off target delivery compared to current targeting techniques. The concept has been validated in vitro using single chain variable fragments (scFv), derived from antibodies as model affinity domains. Using this approach, gene sequences encoding scFvs were genetically fused to gene sequences encoding the platelet-derived growth factor receptor transmembrane domain, to facilitate display on the surface of multiple subsets of EVs. Constructs include affinity tags on both termini of the fusion protein to enable verification of full length protein display and surface localization. EVs were harvested from HEK293FT cells and Western Blot analysis was used to confirm that EVs contained the desired targeting moiety. This method provides a superior alternative to current techniques used to generate EVs and has the potential to enable EV-based therapeutics for a broad range of therapeutic applications.
- *Inventors
- Joshua Leonard*Devin Stranford
- *Publications
- Stranford DM & Leonard JN (2017) Chapter Five - Delivery of Biomolecules via Extracellular Vesicles: A Budding Therapeutic Strategy, in Advances in Genetics, T. Friedmann, J.C. Dunlap, and S.F. Goodwin, Editors., Academic Press. 155-175.
- 國家/地區
- 美國
