Functional delivery of lipid-conjugated siRNA by extracellular vesicles
Extracellular vesicles (EVs) are cell-derived, membranous nanoparticles that mediate intercellular communication by transferring biomolecules, including proteins and RNA, between cells. As a result of their suggested natural capability to functionally deliver RNA, EVs may be harnessed as therapeutic...
| Principais autores: | , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
Elsevier
2017
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| _version_ | 1826282029164003328 |
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| author | O'Loughlin, A Mäger, I de Jong, O Varela, M Schiffelers, R El Andaloussi, S Wood, M Vader, P |
| author_facet | O'Loughlin, A Mäger, I de Jong, O Varela, M Schiffelers, R El Andaloussi, S Wood, M Vader, P |
| author_sort | O'Loughlin, A |
| collection | OXFORD |
| description | Extracellular vesicles (EVs) are cell-derived, membranous nanoparticles that mediate intercellular communication by transferring biomolecules, including proteins and RNA, between cells. As a result of their suggested natural capability to functionally deliver RNA, EVs may be harnessed as therapeutic RNA carriers. One major limitation for their translation to therapeutic use is the lack of an efficient, robust and scalable method to load EVs with RNA molecules of interest. Here, we evaluated and optimised methods to load EVs with cholesterol conjugated small interfering RNAs (siRNAs) by systematic evaluation of the influence of several parameters, including incubation time, volume, temperature, and EV:cc-siRNA ratio. EV loading under conditions that resulted in the highest siRNA retention percentage, incubating 15 molecules of cc-siRNA per EV at 37 °C for 1 hour in 100 µl, facilitated concentration dependent silencing of HuR, a therapeutic target in cancer, in EV-treated cells. These results may accelerate the development of EV-based therapeutics. |
| first_indexed | 2024-03-07T00:37:42Z |
| format | Journal article |
| id | oxford-uuid:81fd4d59-bf5e-4b4c-9f1f-d5c057d9939b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:37:42Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:81fd4d59-bf5e-4b4c-9f1f-d5c057d9939b2022-03-26T21:34:08ZFunctional delivery of lipid-conjugated siRNA by extracellular vesiclesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:81fd4d59-bf5e-4b4c-9f1f-d5c057d9939bEnglishSymplectic Elements at OxfordElsevier2017O'Loughlin, AMäger, Ide Jong, OVarela, MSchiffelers, REl Andaloussi, SWood, MVader, PExtracellular vesicles (EVs) are cell-derived, membranous nanoparticles that mediate intercellular communication by transferring biomolecules, including proteins and RNA, between cells. As a result of their suggested natural capability to functionally deliver RNA, EVs may be harnessed as therapeutic RNA carriers. One major limitation for their translation to therapeutic use is the lack of an efficient, robust and scalable method to load EVs with RNA molecules of interest. Here, we evaluated and optimised methods to load EVs with cholesterol conjugated small interfering RNAs (siRNAs) by systematic evaluation of the influence of several parameters, including incubation time, volume, temperature, and EV:cc-siRNA ratio. EV loading under conditions that resulted in the highest siRNA retention percentage, incubating 15 molecules of cc-siRNA per EV at 37 °C for 1 hour in 100 µl, facilitated concentration dependent silencing of HuR, a therapeutic target in cancer, in EV-treated cells. These results may accelerate the development of EV-based therapeutics. |
| spellingShingle | O'Loughlin, A Mäger, I de Jong, O Varela, M Schiffelers, R El Andaloussi, S Wood, M Vader, P Functional delivery of lipid-conjugated siRNA by extracellular vesicles |
| title | Functional delivery of lipid-conjugated siRNA by extracellular vesicles |
| title_full | Functional delivery of lipid-conjugated siRNA by extracellular vesicles |
| title_fullStr | Functional delivery of lipid-conjugated siRNA by extracellular vesicles |
| title_full_unstemmed | Functional delivery of lipid-conjugated siRNA by extracellular vesicles |
| title_short | Functional delivery of lipid-conjugated siRNA by extracellular vesicles |
| title_sort | functional delivery of lipid conjugated sirna by extracellular vesicles |
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